Thread: L-dopa

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    Default L-dopa

    L-Dopa is an amino acid supplement that produces dopamine in the body after oral ingestion.

    L-Dopa is found in:

    Mucuna Pruriens*(Young seeds have 53.31+/-0.03mcg/g (0.53%) to 119.2 ± 6.9mcg/g (1.19%))[1][2]*Seeds tend to increase in L-Dopa content as they mature, up to an average of 3.1-6.1% with the highest recorded value of 9%.[3][4]*Leaves of M.Pruriens have around 0.5%.[5]

    Generally high in all members of the Mucuna family, including Holtonii (6.13-7.5%), Andreana (6.3-8.9%), Aterrima (3.31-4.2%) and Gigantean (1.5-3.78).[6][7]

    Tamarindus indica (Seeds have 377.6 ± 13.9mcg/g, or 3.78%)[1]

    Sesbania bispinosa (Seeds have somewhere around 425.6 ± 25.0mcg/g (4.25%) or 2.01%)[1][8]

    Entada scandens (Seeds have 167.2 ± 6.9mcg/g, or 1.67%)[1]

    Acacia leucophloea (Seeds have 239.7 ± 62.8mcg/g, or 2.39%)[1]*although sometimes there is none.[9]

    Bauhinia variegata (Seeds have 291.2 ± 6.9mcg/g, or 2.91%)[1]

    Canavalia gladiata (Seeds have 422.4 ± 12.0mcg/g, or 4.22%)[1]

    Vigna aconitifolia, unguiculata, and vexillata at around 0.2-0.58%[6]

    Prosopis Chilensis[6]

    The exact number in the sources are variable, as is the nature of plants. The general notion should be that C.Gladiata, T.Indica, and S.Binpinosa appear to be quite high as well as*Mucuna Pruriens; the standard source of L-Dopa in supplements.

    1.2. Structure and Physicochemical Properties

    L-Dopa, when oxidized, can form bonds with sulfur containing compounds (such as cysteine) to polymerize with other amino acids and lower bioavailability of protein when L-Dopa is consumed via foods.[2]

    L-Dopa can be destroyed in legumes by cooking and soaking with alkaline solutions.[4][2]*Although it can also be destroyed with basic cooking, toasting does not appear to destroy L-Dopa from*Mucuna Pruriens.[10]

    2Pharmacology

    2.1. Absorption

    Chronic usage of L-DOPA is associated with a greater bioavailability of future L-DOPA ingestion.[11]

    3Interactions with Hormones

    3.1. Androgens

    A dose of 1000mg/kg bodyweight L-DOPA in rats (human dose equivalent 160mg/kg) is associated with an increased circulating testosterone level in rats after 7-14 days, possibly secondary to Luteinizing Hormone.[12]*The only other study investigating testosterone levels is one done in Japanese Quails, which shows increased testosterone possibly secondary to dopaminergic influence of the testes.[13]

    The theory of dopamine precursors increasing testosterone is there, but the topic has not been investigated into with any depth.

    3.2. Growth Hormone

    0.5g L-DOPA has been associated with increasing levels of circulating growth hormone in persons without hypopituitarism, with the Tmax*being approximately 60 minutes after ingestion.[14]*This increase in growth hormone has been replicated elsewhere.[15]

    3.3. Luteinizing Hormone

    In rats, an oral dose of 1000mg/kg bodyweight (human dose equivalent 160mg/kg) increases Lutenizing hormone after 4 hours yet it returns to baseline after 8 hours.[12]*This effect was not seen at 200mg/kg (32mg/kg humans) nor any dose below[12], ingestion of 500mg L-DOPA in humans, according to one study, actually causes a slight but significant decrease in circulating Luteinizing Hormone levels over the 2 hours following treatment.[15]

    3.4. Cortisol

    One study measuring cortisol levels after ingestion of 500mg L-DOPA found that the decrease seen in cortisol was not significantly different from placebo.[15]*A more recent study in persons with Parkinson's disease suggests a reduction in cortisol levels after ingestion of 200mg L-DOPA (paired with 50mg benserazide).[16]

    4Sexuality and Pregnancy

    4.1. Penile Tissue

    L-DOPA administration at 800mg daily for 7 days in healthy men (no complaints of penile problems) is associated increased penis tumescence (thickness from bloodflow); however, its effects were most significant when serum testosterone was greater than 17.5pg/mL suggesting the effect is androgen-dependent.[17]*In youth (20-30) it also increased maximum penile girth.[17]*This effect may be mediated through dopamine receptor agonism.[18]

    Increased dopamine appears to increase thickness of the flaccid penis, and this applies to L-DOPA supplementation due to increasing dopamine. There are no studies on erect penis thickness

    4.2. Libido

    Interestingly, with Levodopa therapy in Parkinson's Disease a possible side-effect is Hypersexuality associated with excessive dopaminergic firing via dopaminergic agonism.[19]It is more commonly associated with chemical dopamine agonists rather than levodopa, however. It is one of the many side effects associated with compulsivity from dopamine agonism, just the sexual manifestation.[19][20]

    In healthy men and women, 100mg single administration of L-DOPA was able to augment magnitude of T-reflex (used to measure physical responses to orgasm) in men, although 100mg L-DOPA was ineffective at increasing libido or sexual arousal;[21]*possibly related to dopamine's role in the energetic aspects of motivated behaviour,[22]by acting on the oxytocinergic neurons in the PVN of the hypothalamus.[23]*3 men reported penile erection during the control (non-sexual) film used, an amusing side-effect.

    Case studies of persons using L-DOPA at dosages exceeding 2.5g note hypersexuality and more frequent (sometimes inappropriately timed) erections, although this subset of case studies are intertwined with psychiatric disorders. Dosages exceeding 6g were associated with increased aggressiveness.[24]

    Dopamine is definitely involved in Libido and the physical response to sexual excitation, although L-DOPA treatment may not be potent enough to be clinically relevant in isolation it may be valuable in combination with other compounds. Whether L-DOPA supplementation will lead to increase sexuality in otherwise healthy persons is not known.

    5Other Medical Conditions

    5.1. Polycystic Ovarian Disease (PCOS)

    Women who have PCOS (excess circulating androgen levels) may alter the effects of oral L-DOPA on hormones, lowering the increase in growth hormone seen after L-DOPA in women without PCOS.[25]*Interestingly, these effects are also seen in obese individuals.[26]*The former conditions is characterized by higher insulin and IGF-1 levels, which may play a role.[25]*The latter conditions, obesity, seems to reduce the GH secretion from L-DOPA via elevated serum fatty acids (triglycerides). These elevated TGs hinder growth hormone secretion at rest[27]*and reducing their levels can enhance the efficacy of compounds that stimulate GH release.[28]

    6Nutrient-Nutrient Interactions

    6.1. COMT inhibition

    L-DOPA is rapidly converted into dopamine in peripheral tissue (ie. not the brain) via dopamine decarboxylase enzymes, and this is the reason for its common therapeutic pairing with carbidopa; under these conditions, the next major pathway that mediates conversion of L-DOPA (albeit a methylation process to 3-O-methyldopa) would be via catechol-o-methyltransferase (COMT) which EGCG from the*green tea catechins*is known to inhibit[29]*and in some patients pharmaceutical COMT inhibitors such as tolcapone or entacapone are also recommended.[30][31]

    It seems many COMT inhibitors can suppress this secondary conversion of L-DOPA into 3-O-methyldopa, including (+)-catechin (3.7+/-3.2μM[32]), (-)-epicatechin (10.7+/-6.7μM[32]), and*quercetin*(1.9+/-0.4μM[32]) although only (+)-catechin worked*in vivo*at 400mg/kg injections where L-DOPA concentrations in plasma are unaffected yet 3-O-methyldopa is decreased.[32]

    It seems that after the dopamine decarboxylase enzymes are taken care of, the COMT enzyme may become (relatively) more active and methylate L-DOPA. COMT inhibitors such as EGCG or (+)-catechin can reduce this reactions

    6.2. S-Adenosyl Methionine

    S-adenosyl Methionine*(SAMe) is a small molecule involved in a process known as methyl donation, seen as an intermediate in one pathway of cellular maintenance.

    One study in children with a dopamine deficeincy being treated with Levodopa noted that supplementation of Levodopa caused a decrease in concentrations of SAMe in cerebrospinal fluid with an increase in 3-methoxytyrosine.[33]

    7Safety and Toxicology

    7.1. Drug-Induced Dyskinesia

    L-DOPA is able to cause abnormal motor control (Drug-Induced Dyskinesia), which is seen as a common side effect when L-DOPA is used chronically for treating Parkinson's Disease. A loss of Dopamine in the Basal Ganglia (a brain structure) is associated with a process called dyskinogenesis; the production of dyskinesia, or involuntary movement of skeletal muscles.[34]*

    Dyskinesis is associated with an increased expression of*dynorphin*in the striatum[35]*and increases of the mRNA of both preproenkephalin A and prodynorphin (preproenkephalin B) in the striatum.[36][37][38]

    On the neuronal side of things, it is hypothesized that drug-induced dyskinesia is due to sensitization of the D1 (dopamine-1) receptors on the MSN neurons in the striatum.[39]*High sensitization leads to intermittent and excessive cAMP signalling cascades, and involuntary movement.

    Interestingly, tolerance to*caffeine*is associated with desensitized D1 receptors on this neuronal cluster and may be used to manage symptoms of involuntary motor control associated with L-DOPA supplementation.[40]

    For healthy persons, the importance of being concerned with Levodopa induced dyskinesia is unknown. The chance of dyskinesia appears to increase with disease pathology, and correlates with destruction of dopamingergic neurons typical of Parkinsons and age; increasing from 40% to 80% over the course of 5 years of Parkinsons.[41]In primates it has been shown that dyskinesia is not induced in healthy controls at the same dose that induces dyskinesia in those with less dopaminergic neurons and Parkinsons progression.[42]*Another study done on squirrel monkeys suggested that nigrostriatal dopaminergic neuron loss is a prerequisite for dyskinesia, and that Levodopa-induced dyskinesia can not occur in healthy controls.[43]*

    Major concern associated with L-DOPA, but appears to pretty much only be relevant to those suffering from Parkinson's Disease or similar neurodegeneration. Most likely not a concern for healthy persons using L-DOPA in moderation



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    Something new for me, thank you. Need to try
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    More penile girth , count me in!
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    L-dopa

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    So I went back and read this thoroughly and have to say that’s a kick ass explanation on various l-Dopa findings!

    Im not sure I read this right though as it sounds counter intuitive:
    Chronic usage of L-DOPA is associated with a greater bioavailability of future L-DOPA ingestion

    So the longer you take this, results in more bioavailability?? You would think the opposite would be true , at least I would.
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    L-dopa, velvet bean, dopadex etc is in alot of supplement blends I used used to alot!!


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    Just ordered some of this, how much are you taking a day brother?
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    Too funny, i too was going to look into where i could get this, although i havent looked yet. Kind of funny though they had to make note to reader that Gerth was not measured in erect penises lmao, Nows theres a study i would pay to watch, in a none gay way, if thats even possible lmao
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    Quote Originally Posted by blacktail View Post
    Just ordered some of this, how much are you taking a day brother?
    I am not cause I am using MC Anti-P
    (Cabar)
    But I do take it. Think 500-1000mg at night.
    But wait till later gonna check label and be sure

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    Bottle says 333mg in morning and afternoon I always used at night.
    Normally between 500mg and 750mg depending on dosed caps!
    Quote Originally Posted by Muscle mechanic View Post
    I am not cause I am using MC Anti-P
    (Cabar)
    But I do take it. Think 500-1000mg at night.
    But wait till later gonna check label and be sure

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    Quote Originally Posted by Muscle mechanic View Post
    I am not cause I am using MC Anti-P
    (Cabar)
    But I do take it. Think 500-1000mg at night.
    But wait till later gonna check label and be sure

    Sent from my SAMSUNG-SM-G890A using Tapatalk
    I'm currently also taking Anti-P, should you not take them both at the same time?
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    Quote Originally Posted by blacktail View Post
    I'm currently also taking Anti-P, should you not take them both at the same time?
    I wouldn't
    But they combine them with Parkinson's with something else.
    But we don't have Parkinson's
    So we take at Lower dose.
    Dopamine is good but I wouldn't over do it.
    I use L-dopa when off Cabar or anti-p!!
    Doesn't hurt to look into it

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    Last edited by Muscle mechanic; 09-13-2018 at 09:23 PM.
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    "Increased dopamine appears to increase thickness of the flaccid penis, and this applies to L-DOPA supplementation due to increasing dopamine."

    Sign me up..
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    Quote Originally Posted by chihuahua View Post
    "Increased dopamine appears to increase thickness of the flaccid penis, and this applies to L-DOPA supplementation due to increasing dopamine."

    Sign me up..
    Me too
    Just a grateful member!!

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