1.Sources and Composition
1.1. Sources
Mucuna Pruriens is a plant from India, the Caribbean or Arfica. It is a climbing shrub that has the ability to grow white, lavender, or purple flowers and causes itching upon physical contact with the outer hairs and skin. Like most herbal supplements, it possess an anti-oxidant content.[1]Mucuna is actually a legume, and thus has a caloric content. Beside the nutraceutical content below, mucuna (velvet) beans contain 20-35% protein by total caloric content.[2] Mucuna also contains protein digestive enzyme inhibitors, which can be reduced with processing.[3] Soaking in bicarbonate (following by autoclaving or cooking) has been shown to reduce a wide variety of anti-nutrients in Velvet beans, but also reduces levodopa content, the active ingredient.[4]
1.2. Composition
Mucuna Pruriens contains:- L-DOPA, or Levodopa, the precursor to dopamine and seen as the main constituent[5] and eventually adrenaline. The three catecholamines are also present in Mucuna[6]
- Nicotinic Acid[7]
- Tetrahydroisoquinoline alkaloids in dosages of 8-24mg/500g dried milled seeds, which may have interactions with u-opioid receptors based on their structures.[8]
- Serotonin and its precursor, 5-HTP
- NN-dimethyltryptamine and 5-MeO-dimethyltryptamine (bufotenin) in the seed.[9]
- Beta-Carboline[10]
- Mucunain, a compound that causes itches when skin comes into contact with Mucuna species
- Various saponins, anthraquinones, flavonoids, terpenoids, cardiac glycosides and tannins[1]
- A glycoprotein inhibitor of protein digestive enzymes[11]
- Behenic Acid, a dietary fatty acid with low bioavailability[12]
- In the cotyledon of the plant, CoQ10 and Nicotine adenine Dinucleotide (NADH).[7]
- D-chiro Inositol (2.1+/-0.2mg/g) and two storage forms of it (galactose glycosides; 11.4 and 21.2mg/g), also myo-inositol (8.2+/-0.6)[13]
- Basic dietary minerals in small amounts, such as Selenium, Iron and Magnesium[12]
Tryptamine compounds (hallucinogenic compounds) are at rather low dosages in the leaves and non-existent in the seeds; 0.006% Dimethyltryptamine, 0.0025% 5-MeO-Dimethyltryptamine, and 0.003% Dimethyltryptamine Oxide.[14] 5-MeO-Dimethyltryptamine (Bufotenin) has been noted to be as high as 4.14ug/g in the root, but was not present in the pod.[18]
2. Pharmacology
When measuring the L-Dopa (Levodopa) in the bloodstream after ingestion of 15g or 30g of Mucuna Pruriens, the AUC 16,306+/-4024 and 43,087+/-9735ng/h/mL respectively (whereas standard L-dopa/carbidopa 200mg/50mg was 16,243+/-2543), the Cmax was 8,607+/-1979ng/mL and 14,606ng/mL respectively (standard was 6596+/-1098), the Tmax was 61.8+/-12.9 minutes and 72.5+/-15.1 minutes respectively (standard was 95.5+/-10.5 minutes) and half-life was 58.6+/-5.1 minutes and 94+/-25.5 respectively (standard was 90.8+/-23.8).[19] Statistically different results were seen with 30g Mucuna having a larger AUC and Cmax and 15g Mucuna having significantly less of a half-life.[19]Measured AUC of 3-O-methyldopa was not significantly different between standard treatment (24,267+/-4559 ng/h/mL) and 30g Mucuna (22,698+/-2833 ng/h/mL) but was significantly less for 15g Mucuna (20,292+/-283.3 ng/h/mL).[19]
2.1. Comparisons against Levodopa
Levodopa treatment is the standard therapy used for treatment of Parkinson's symptoms. It is generally seen as preferred as it is one molecule and can be studied better than Mucuna Pruriens, which is sometimes seen as a highly variable cocktail of many ingredients with unknown interactions.It has been suggested that although Levodopa per se can increase DNA damage through copper ions in the brain, some other compounds in Mucuna alleviate this damage via exerting a metal chelating effect.[20] This insinuates less potential DNA damage from copper ion excess with Mucuna relative to Levodopa. The general co-ingestion of anti-oxidants alongside metal chelators may confer additional protection.[21]
At least one human study on Mucuna Pruriens compared its results to standard Levodopa treatment and noted less occurance of dyskinesia.[22] It is not sure whether this is due to the above protective mechanisms, or due to Levodopa from Mucuna Pruriens being more bioactive. Levodopa in Mucuna Pruriens appears to be 2-3x more bioactive (potent) when compared to the same dose of isolated Levodopa, which is hypothesized to be due to a currently unknown Dopamine Decarboxylase inhibitor in Mucuna Pruriens.[22] Standard Levodopa therapy for Parkinsons tends to pair it with Carbidopa to inhibit this enzyme and prolong the effects of Levodopa.
Levodopa and Mucuna Pruriens both seem effective. In isolation, Mucuna Pruriens may be better (due to the fact that it, as a herb, is never a molecule in isolation), but no studies exist comparing Mucuna to Levodopa and Carbidopa. The above studies suggest that Mucuna can hold its ground against standard Levodopa/Carbidopa therapy, but doesn't suggest it is better.
3. Interactions with Hormones
3.1. Dopamine
Mucuna Pruriens supplementation has been shown to increase circulating dopamine levels in otherwise healthy male controls, possibly through the main ingredient of levodopa.[23]3.2. Prolactin
Mucuna Pruriens has also been shown to suppress Prolactin levels in vivo, supposedly vicariously through Dopamine's ability to suppress prolactin secretion.[23][24]3.3. Testosterone
Testosterone has been increased in healthy infertile men without any impairments in seminal parameters following 5g of Mucuna Pruriens extract over 3 months.[23] Testosterone was also increased in the seminal experimental groups (those with low sperm motility or count), and to a more significant degree. Testosterone levels in the control (no sperm problems, still infertile) group went from 4.49 ± 0.53 to 5.72 ± 0.36ng/mL. The hypothesized mechanism of action was through levodopa content, in which the increase in serum dopamine antagonizes (works against) prolactin's suppressive effect on libido and testosterone.[23]In rats with type II diabetes, increases in testosterone have been seen with an oral dose of 200mg/kg bodyweight Mucuna Pruriens[25] or in blend with two other aphrodisiac herbs.[26]
Only one human study, and it increased testosterone in infertile men. It is not known whether it can increase testosterone in already fertile men.
4. Interactions with Glucose Metabolism
4.1. Results of interventions
Mucuna Pruriens has been investigated in rats for its anti-diabetic effects. It appears to reduce spikes in blood glucose in response to a meal up to 8 hours after ingestion in a relatively dose-dependent manner, with descending efficacy.[27] At 7 different oral dosages ranging between 5-100mg/kg bodyweight, blood glucose was reduced by 18.6%-55.4%.[27] Previous studies on the subject matter noted clinically relevant benefits only after 15 days at an oral dose of 200mg/kg bodyweight in rats[28], the differences between the two studies, as mentioned by the chronologically later study, may be due to chance variation in growing conditions.[27]Chronic usage of Mucuna for blood sugar reduction appears to be more potent than acute usage, although both are effective.[28] An oral dose of 5mg/kg bodyweight in rats is associated with a 55.3% reduction in blood sugar after 12 weeks, but acutely reduced blood sugar by 18.6%.[27] The efficacy of 50mg and 100mg/kg bodyweight are not significantly different from an oral dose of 5mg/kg bodyweight Glibenclamide (diabetic drug) in rats.[27] Potent effects on suppressing blood glucose may appear in as little as one month, although it seems to be somewhat maxed out at this time as evidence by one study investigating Mucuna supplementation at 1 and 2 months, and finding reductions of 38.01% and 40.41% at 1 and 2 months, respectively.[29]
The blood glucose lowering effect does not require diabetes as a pre-requisite, and is effective in normal rats as well.[30]
4.2. Diabetic management
Mucuna Pruriens shows efficacy in reducing the onset of diabetic cataracts in experimental rats,[29] its influences on nerve damage in diabetic rats does not appear to be significant.[31] Although Mucuna Pruriens may suppress a rise in urinary albumin levels associated with diabetes, it fails to prevent the hypertrophy of the kidneys associated with diabetes.[32]4.3. Mechanisms and theories
When looking at liver enzymes involved in carbohydrate metabolism, one study in streptozotocin-induced diabetic rats noted that the normal suppression associated with diabetes was partially reversed with Mucuna Pruriens. Glucokinase decreased by 78.08% in diabetes, increased by 23.96% with Mucuna plus diabetes yet increased only 0.31% in normal rats. Hexokinase decreased by 51.93% with diabetes, increased 53.17% with Mucuna plus diabetes, and decreased by 6.89% in normal rats. Finally, Glucose-6-phosphatase was decreased by 60.36% in diabetes, increased by 128.47% in Mucuna plus diabetes, and increased 23.84% in normal rats (all effects at 200mg/kg bodyweight in rats).[28]It is not known what causes these effects, but a hypothesis is the D-chiro inositol content.[13] With a content of about 2.1+/-0.2mg/g in Mucuna Pruriens, the dosages used in the above studies nears 7mg which is in the lower range of effectiveness in studies looking at pure D-chiro Inositol.[33][34]
5. Interactions with Neurology
5.1. Parkinsons and Dopamine
Mucuna Pruriens is being investigated for its ability to alleviate symptoms of or to treat Parkinson's Disease. At this moment in time, only one double blind study has been conducted on humans.[19] A rather large dose of Mucuna, 15-30g daily (4.86% Levodopa; ended up being 500-1000mg Levodopa daily), was equally effective as standard Levodopa/Carbidopa (200mg/50mg) treatment in treating symptoms of Parkinson's Disease.[19] A rat study investigating the same question found that low dose Mucuna paired with benserazide (peripheral dopa-decarboxylase inhibitor) was able to suppress symptoms associated with Parkinsons while low dose Levodopa + Benserazide was not; additionally, long-term usage of Mucuna Pruriens was more effective than long-term usage of Levodopa in isolation, when both were contributing the same dose of Levodopa.[22] The differences seen were suggested to be due to a possible Dopa-decarboxylase inhibitor in Mucuna Pruriens. Other studies comparing Levodopa to Mucuna also note this difference, and suggest that one needs thrice as much Levodopa in isolation to match Levodopa from Mucuna.[15]Beyond the double blind study mentioned, three open label studies in humans have been conducted.[35][36][37] Over a period of 12 weeks with 45g Mucuna Pruriens (1500mg Levodopa equivalent) was found to improve symptoms of Parkinsons.[37]
The levodopa content has carryover to other dopamine-related conditions, such as suppression of tardive/orofacial dyskinesia symptoms.[38] Doses as low as 48mg/kg Mucuna in rats (6% Levodopa) reduces tacrine-induced spontaneous jaw movements, an animal model for tardive dyskinesia.[15] This dosage is approximately 8mg/kg bodyweight after conversion to human dosages based on Body Surface Area, or 730mg daily for a 200lb person.
Mucuna Pruriens definitely appears to have interactions with Parkinson's Disease, although its exact role (treatment, adjunct therapy, preventative medicine) is not fully examined. It looks to be a highly promising herbal.
5.2. Memory and Cognition
Mucuna Pruriens has been involved in a blend of herbs (n=11) that increased memory retention in rats, but was too confounded to place any causation on Mucuna.[39]5.3. Neuroprotection
One in vitro study suggests that Mucuna Pruriens extract increased the activity of complex I in brain mitochondria.[7]Mucuna Pruriens was also found to restore levels of serotonin and catecholamines in the substantia nigra (area of the brain associated with Parkinson's), whereas isolated levodopa was not able to do this.[7]
5.4. Libido and Fertility
Mucuna Pruriens supplementation in infertile men is associated with increased sperm count and motility after taking 5g of dried powder for 3 months.[23] This same dose also increases various parameters of male semen indicative of increased fertility.[40][41]In regards to testosterone, one study noted it could be increased over 3 months after ingestion of 5g Mucuna Pruriens seed powder daily; however, this study was conducted in infertile men and the increases seen did not exceed control.[40]
In rat studies looking at sexuality, mounting frequency is significantly increased at 150-250mg/kg bodyweight in rats;[42] a dose of 2.4-4mg/kg bodyweight in humans assuming standard Body Surface Area conversions.[43] Similar results have been seen in rats with type II diabetes induced by streptozotocin at a dose of 200mg/kg bodyweight[25] and the same dosage/animal model of diabetes was found to alleviate damage on penile tissue associated with diabetes, suggesting preservation of sexuality in response to a disease state.[44]
Appears to be effective in increasing sperm parameters and libido in studies on infertile men, but the evidence for its usage in otherwise healthy persons is less robust. It might be effective, but it really isn't known for sure.
6. Protease Inhibition
6.1. Anti-venom
Mucuna Pruriens has been traditionally used as an anti-venom agent, specifically against the venom of Echis carinatus (a snake).[45][46]This protection from venom appears to be mediated through a protease inhibitor; normally seen as a negative due to preventing absorption of dietary protein, the specific glycoprotein in Mucuna Pruriens can degrade the toxin from this snake as said toxins are quaternary proteins.[11][47][48] Mucuna Pruriens shows efficacy against EC toxin either when pre-loaded or as a single bolus in rats.[49]
6.2. Digestion
As a protease inhibitor, the glycoprotein from Mucuna can inhibit the two main human gastric protein digestive enzymes of trypsin and chymotrypsin in a dose-dependent manner.[50][11] It belongs to the Kunitz family of trypsin inhibitors.[38]The glycoprotein inhibitor appears to be most stable at pHs of 4-7[11] and have structural similarities to the protease inhibitor found in soy.[47] The inhibitory amounts are maxed at 61.5% for trypsin and 47.9% for chymotrypsin, with slightly higher values for whole Mucuna protein extract rather than isolated glycoprotein.[11]
All inhibitory potential is lost at 100°C, and efficacy starts to be lost at 50°C, Increasing the pH to 9-12 can destroy the protein at temperatures of 75°C.[11] Protein digestability also increases when exposed to irradation in a dose-dependent manner.[12] Irradiation may decrease Manganese and Sodium content slightly and reduced caloric content on a basis of dry weight slightly.[12]
The above trypsin inhibitor is the same kind of 'evil' compound found in foods like soy that reduce protein absorption, and thus cooking Mucuna beans would be smart for the protein content. If you are buying powdered Mucuna Pruriens supplements, it would probably be prudent to look for roasted supplements, as cooking them normally destroys L-DOPA. The study on irradiation did not measure L-DOPA.
7. Safety and Toxicity
One large double blind study noted no significant adverse effects from 15-30g of Mucuna Pruriens powder over the course of 12-20 weeks aside from one patient suffering from vomiting, which was deemed unrelated to the bioactivity of Mucuna but rather its digestability and palatability.[19]In rats, doses of 32mg/kg or above are associated with 'some adverse side effects' (hyperventilation, reduced spontaneous motor activity, spontaneous erections) that appeared 1 hour after ingestion transiently, and doses up to 100mg/kg are free from more significant side effects for up to 12 weeks (study termination).[27]