Due to a long stint of drug abuse in my early twenties (some adderall and cocaine) and lifestyle (TV, video games, porn, internet), I'm setting out to "repair" the dopamine system in my brain with supplements.
Currently I'm working on a system to track markers of long-term, sustained dopamine upregulation: mood, productivity, and subjective well-being.
Here's what I'm stacking at the moment (rationale/literature for each is below):
- R-ALA
- Uridine
- Vitamin B12, Trimethylglycine, and 5-MTHF
- Vitamin B6, Vitamin C, Selenium
- Wild green oat extract / avena sativa
- N-Acetyl L-tyrosine
- Mucuna pruriens
- L-Phenylalanine
- Maca
I'm currently testing optimal dosing and frequency of each, and whether the effects of individual supplements have synergistic or inhibitory effects.
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R-ALA
via DHA & EPA
ALA is the parent compound of Omega 3 and can be converted by enzymes into the longer chain Omega 3 fatty acids EPA (eicosapentaenoic acid) and DHA (docosaheaxaenoic acid). [source]
I've chosen ALA over EPA and DHA because it can be purchased as a solid, and thus potentially mixed in with other ingredients in a stack.
The conversion of the plant-based omega-3 ALA to the long-chain EPA and DHA may be increased in vegans and vegetarians who do not eat fish, suggest results from the European Prospective Investigation into Cancer and Nutrition (EPIC). [source]
EPA and DHA shown to have benefits in regulating the dopamine pathway in rats. [sources: 1, 2, 3, 4]
Uridine + DHA shown to benefit Parkinson's patients: "oral administration of the phosphatide precursors uridine and DHA can ameliorate the impairment in dopaminergic terminals and transmission in 6-OHDA-lesioned rat striata, probably by increasing the amount of synaptic membrane generated by surviving striatal neurons." [source]
Uridine
Rats given uridine-5′-monophosphate had increased acetylcholine and dopamine. [sources: 1, 2]
The chemical uridine promotes the creation of new dopamine receptors in the brain, an effect which is more pronounced in brains with fewer dopamine receptors. This is done by activating the D1 and D2 receptor signaling cascade, which stabilizes spikes of dopamine activity that would normally “burn out” receptors and reduce their effective number. Modulation also increases the rate of new receptor formation in areas where they are less dense, effectively increasing the number and density of dopamine receptors. Choline – particularly CDP-choline – also has the potential to increase dopamine receptor density. [source]
Though, the reported effects on dopamine receptor up-regulation may be short lived.
Vitamins B12, 5-MTHF & Trimethylglycine
Contribute to and regulate the SAM cycle. Rationale for choosing precursors over direct SAMe given here by Abelard Lindsay:
Adding SAM-e directly would, in my opinion, be suboptimal as research shows it does not do anything to lower homocysteine levels]. Providing highly bioactive forms of b-vitamins involved in the conversion of homocysteine to SAM-e and L-Cysteine and adding betaine to help methylate homocysteine would seem to be the most optimal route to optimizing the SAM cycle and there is research to support this.
D4 receptor methylation activity is influenced by the availability of 5-MTHF, (5 methyl tetrahydrofolate), the active form of folate. If there is not enough 5-MTHF present, then dopamine receptors will not be activated... even if there are high levels of dopamine present. [ref]
Point of concern: it's possible to take too much folic acid, and it also interacts with certain drugs.
Vitamins B6, C & Selenium
Essential vitamins contributing to dopamine production:
Vitamin B6 helps convert L-Dopa into dopamine, Vitamin C helps convert dopamine into norepinephrine (increasing alertness and attention), and selenium protects brain cells while regulating the amount of dopamine-producing enzymes in the brain. Each of these also have important antioxidant properties that protect cells from damage during the production and metabolism of dopamine. [ref]
Evidence here is inconclusive and insubstantial, especially for long-term studies:
It appears that the cognitive benefit of acute WGOE supplementation does not persist with chronic treatment in older adults with normal cognition. It remains to be seen whether sustained effects of WGOE supplementation may be more evident in those with mild cognitive impairment. [source]
LE sells this as "Dopa-Mind" but I haven't tried it myself. Like others, I'm dubious about WGOE.
N-Acetyl L-Tyrosine (NALT)
A good source of L-DOPA, and contains some other molecules that may aid the benefits of L-DOPA.
Two benefits here worth noting, via Examine:
"The reduction in dopamine seen in infertility seems to be reversed with L-DOPA ingestion; theoretically L-DOPA ingestion should unilaterally increase dopamine."
"Possible symptoms reduction in Parkinson's Disease related to the L-DOPA content and theorized (but not proven) peripheral dopamine decarboxylase inhibitor; this is notable as a L-DOPA and carbidopa combination supplement is the reference for reducing parkinson's symptoms."
A precursor to L-Tyrosine, which is converted to dopamine in the brain.
Maca
Activates the dopaminergic system, increases libido.
"In mouse brain tissue, after six weeks of treatment, noradrenaline and dopamine levels were increased by maca extract, and the activity of reactive oxygen species was significantly inhibited. Serotonin levels were not significantly altered. These results demonstrated that maca extract (250 and 500 mg/kg) showed antidepressant-like effects and was related to the activation of both noradrenergic and dopaminergic systems, as well as attenuation of oxidative stress in mouse brain. [source]"
I get a lot of mileage out of maca when used sparingly... once a week or every other week. Beyond that, it tends to slightly depress my mood.