Low dopamine levels can result in reduced cognitive performance and low motivation. They may also explain anhedonia, low libido even in the presence of healthy hormone levels, and general loss of vitality. Mainstream medicine often overlooks correcting low dopamine in part because drugs that increase dopamine tend to actually make people feel better, and may be looked upon with a jaundiced eye as potential drugs of abuse. This concern may be justified, but that does not help people who have low dopamine function and does not excuse failure to address it. Individuals with low dopamine function may as a result seek to remedy the deficit on their own. http://www.mcmanweb.com/dopamine.html
Dopamine is naturally synthesized in the body from amino acids in dietary protein, in particular, phenylalanine and tyrosine. Phenylalanine is an essential nutrient, meaning it is required in the diet in order to sustain life. Tyrosine is present in food and can also be synthesized from phenylalanine. Tyrosine can be converted into levodopa, and levodopa into dopamine. So supplementing with phenylalanine or tyrosine provides the synthesis system with more raw material from which to make dopamine and can increase dopamine levels. Levodopa can also be supplemented in order to increase dopamine levels. Dopamine itself is not normally supplemented because systemic dopamine has other effects that are unwanted and is not generally available to the brain; the brain prefers locally produced dopamine.
Dopamine itself then serves as the precursor to other neurohumors, including norepineophrine and epinephrine. To summarize,
tyrosine -> levodopa -> dopamine -> norepinephrine -> epinephrine
Biochemisty, Lehninger, 1975, p 717.
So to increase dopamine levels, why not just take phenylalanine, tyrosine, or levodopa? These are viable options. There are some caveats, however. Besides serving as a part of structural and functional proteins and as precursor to dopamine, phenylalanine can also be converted into phenylethylamine. Like the other catecholamines cited above, phenylethylamine tends to be stimulating and even anxiogenic. You might want more phenylethylamine or you might not. Tyrosine also is used to make proteins but is otherwise more specific to dopamine and its downstream neurohumors. Levodopa is not used to make proteins and so is still more specific to dopamine and its downstream neurohumors. But because of this more forceful effect, sustained intake of levodopa tends to result in downregulation of dopamine function because the body has few other options to normalize dopamine if there is more than it wants. Levodopa use therefore may lead to tolerance and withdrawal. This same issue is why many dopaminergic drugs have limited utility in application and can be unsustainable approaches to enhancing dopamine function.
In general, we could say that these precursor strategies have limitations because except in the case of nutritional deficiency they don't really address the reasons why dopamine function may be low to begin with. So supplementation of tyrosine or phenylalanine is most helpful in cases of dietary insufficiency, or for temporary use such as during discontinuation of levodopa or other drugs that increase dopamine or other catecholamines.
There are, however, other mechanisms behind low dopamine function. One of broad significance is the tendency for monoamine oxidase B (MAO-B) levels to rise with age. MAO-B is an enzyme that helps regulate dopamine levels by breaking it down. Aging increases MAO-B, which reduces dopamine, and results in the symptoms of low dopamine cited above. Because it gets to the underlying cause of low dopamine function in many people, elevated MAO-B presents itself as an attractive target for intervention.
We could take it a step further and ask what causes MAO-B to increase in the first place, but beyond supporting general brain health and longevity and addressing specific disease states, much more is known about inhibiting MAO-B than addressing the cause of its rise. So for the time being, correcting the MAO-B excess itself is usually the natural intervention closest to the source for people affected by it. What’s more, at least one pharmacologic approach to suppressing excess MAO-B has considerable support in research as a life extension drug, deprenyl. This is a prescription drug and has interaction potential that may contraindicate it for some individuals. So while it may be appropriate for many, natural alternatives are worth exploring.
This is the approach taken by the following study. The researchers developed a rapid screening technique and applied it to 905 natural product extracts, ranking the results by strength of MAO-B inhibition.
Featured Study
Full text link: http://www.ncbi.nlm....les/PMC3521852/
High throughput Screening to Identify Natural Human Monoamine Oxidase B Inhibitors
E Mazzio, S Deiab, K Park, and KFA Soliman
Abstract
Age-related increase in monoamine oxidase B (MAO-B) may contribute to CNS neurodegenerative diseases. Moreover, MAO-B inhibitors are used in the treatment of idiopathic Parkinson disease as preliminary monotherapy or adjunct therapy with L-dopa. To date, meager natural sources of MAO-B inhibitors have been identified, and the relative strength, potency and rank of many plants relative to standard drugs such as Selegiline (L-deprenyl, Eldepryl) are not known. In this work, we developed and utilized a high throughput enzyme microarray format to screen and evaluate 905 natural product extracts (0.025–.7 mg/ml) to inhibit human MAO-B derived from BTI-TN-5B1-4 cells infected with recombinant baculovirus. The protein sequence of purified enzyme was confirmed using 1D gel electrophoresis-matrix assisted laser desorption ionization-time-of-flight-tandem mass spectroscopy, and enzyme activity was confirmed by [1] substrate conversion (3-mM benzylamine) to H202 and [2] benzaldehyde. Of the 905 natural extracts tested, the lowest IC50s [<0.07 mg/ml] were obtained with extracts of Amur Corktree (Phellodendron amurense), Bakuchi Seed(Cyamopsis psoralioides), Licorice Root (Glycyrrhiza glabra/uralensis), Babchi (Psoralea corylifolia seed). The data also show, albeit to a lesser extent, inhibitory properties of herbs originating from the mint family (Lamiaceae) and Turmeric, Comfrey, Bringraj, Skullcap, Kava-kava, Wild Indigo, Gentian and Green Tea. In conclusion, the data reflect relative potency information by rank of commonly used herbs and plants that contain human MAO-B inhibitory properties in their natural form.
The text notes that some natural products were already known or believed to have MAO-B inhibiting activity, calling out two in particular noted in the authors’ own prior research. These were green tea and turmeric extracts, already popular supplements for brain health and longevity. In this current study, however, these extracts were ranked in the second of five levels of MAO-B inhibitive strength. There are reasons for using these supplements aside from MAO-B inhibition, but on that criterion four ranked higher in the first level:
... The herbal extracts showing greatest potency included Amur Corktree (Phellodendron amurense), Licorice Root (Glycyrrhiza glabra and Glycyrrhiza uralensis), Psoralea Fruit (Psoralea corylifolia (PC)) and Bakuchi Seed (Cyamopsis psoralioides)...
There is an important caution. The context of this ranking is solely of screening for MAO-B inhibition. Besides MAO-B inhibition, these herbs have other biological activity that is not investigated by this study, as the authors point out. They may, for example, have MAO-A activity. Compounds which have either MAO-A or MOA-B activity generally have at least some activity on the other, that is, they are not completely selective. Deprenyl is an example; though in low concentration it acts almost solely on MAO-B, at higher concentrations it loses its selectivity and inhibits MAO-A as well. Strong MAO-A inhibitors can lead to severe and potentially fatal illness if used with certain other drugs such as serotonin reuptake inhibitors or foods such as those containing tyramine. The authors state that "future potential drug development should include a tyramine challenge control for in vivo animal studies."
This other biological activity also includes activity unrelated to MAO. Licorice, for example, contains glycyrrhizinic acid, which in excess can cause "hypokalemia and muscle weakness". https://en.wikipedia.../wiki/Liquorice
There is at least one supplement already marketed as an herbal deprenyl alternative, Life Extension’s "Dopa-Mind". It doesn’t use any of the above-mentioned extracts, however, instead using a proprietary avena sativa (wild green oat) extract said to have MAO-B inhibiting activity. The current study lists avena sativa extract in Level 5, indicating it found low MAO-B inhibiting activity. It is possible that the maker of the proprietary extract uses a specific strain and extraction method for increasing this activity, but I have not found any published data to quantify this.
So what do these abilities and limitations add up to? The study authors present their findings as a basis for further research. Based just on the data presented here, however, a combination of small amounts of multiple agents as opposed to larger amounts of one is more likely to be effective in and specific to inhibiting excess MAO-B. In general, all else being equal, multiple agents sharing a common property but having different other properties together would be expected to reinforce the common property while diluting the others.
