The Human Effect Matrix looks at human studies (excluding animal/petri-dish studies) to tell you what effect L-DOPA has in your body, and how strong these effects are.
|Grade||Level of Evidence|
|A||Robust research conducted with repeated double blind clinical trials|
|B||Multiple studies where at least two are double-blind and placebo controlled|
|C||Single double blind study or multiple cohort studies|
|D||Uncontrolled or observational studies only|
Level of Evidence
||Magnitude of Effect Size
An increase in penile girth has been noted in the flaccid state at rest, which is no longer present during sexual stimulation.
No significant influence on libido
L-Dopa is an amino acid supplement that produces dopamine in the body after oral ingestion.
L-Dopa is found in:
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.
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.
L-Dopa can be destroyed in legumes by cooking and soaking with alkaline solutions. Although it can also be destroyed with basic cooking, toasting does not appear to destroy L-Dopa from Mucuna pruriens.
Chronic usage of L-DOPA is associated with a greater bioavailability of future L-DOPA ingestion.
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. 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.
The theory of dopamine precursors increasing testosterone is there, but the topic has not been investigated into with any depth.
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. This increase in growth hormone has been replicated elsewhere.
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. This effect was not seen at 200mg/kg (32mg/kg humans) nor any dose below, 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.
One study measuring cortisol levels after ingestion of 500mg L-DOPA found that the decrease seen in cortisol was not significantly different from placebo. 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).
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. In youth (20-30) it also increased maximum penile girth. This effect may be mediated through dopamine receptor agonism.
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
Interestingly, with Levodopa therapy in Parkinson's Disease a possible side-effect is Hypersexuality associated with excessive dopaminergic firing via dopaminergic agonism. 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.
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; possibly related to dopamine's role in the energetic aspects of motivated behaviour, by acting on the oxytocinergic neurons in the PVN of the hypothalamus. 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.
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.
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. Interestingly, these effects are also seen in obese individuals. The former conditions is characterized by higher insulin and IGF-1 levels, which may play a role. 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 and reducing their levels can enhance the efficacy of compounds that stimulate GH release.
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 and in some patients pharmaceutical COMT inhibitors such as tolcapone or entacapone are also recommended.
It seems many COMT inhibitors can suppress this secondary conversion of L-DOPA into 3-O-methyldopa, including (+)-catechin (3.7+/-3.2μM), (-)-epicatechin (10.7+/-6.7μM), and Quercetin (1.9+/-0.4μM) although only (+)-catechin worked in vivo at 400mg/kg injections where L-DOPA concentrations in plasma are unaffected yet 3-O-methyldopa is decreased.
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
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.
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.
Dyskinesis is associated with an increased expression of dynorphin in the striatum and increases of the mRNA of both preproenkephalin A and prodynorphin (preproenkephalin B) in the striatum.
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. 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.
For healthy persons, the importance of being concerned with Levodopa induced dyskinesia in 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. 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. 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.
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
(Common misspellings for L-DOPA include dopa, ldopa, levdopa, levadopa)