Introduction
There is little doubt that dopamine plays a key role in the symptoms of those of us with a Parkinson’s Disease diagnosis. However, there are now lots of reasons to believe that the old, nocebo effect [negative belief of hopelessness], narrative of “dopamine producing cells dying in the substantia nigra part of the brain” is not the real story.
For example, we have previously explored the biosynthesis of dopamine via the phenylalamine->tyrosine->l-dopa pathway, and seen how this biochemistry can go awry due to reversible chronic stress, nutritional effects, and pathogens, causing apparent dopamine deficits, without needing to resort to the “cell death” narrative.
We have also explored the role of dopamine cell receptors, and seen how the reversible internationalization or sequestration of the cell receptors inside the cell, causes them to then be no longer available for docking with dopamine molecules, making the cells less sensitive to dopamine, rather than cell death per se.
In this follow up article, we will explore the various ways by which dopamine is chemically broken down, degraded, or metabolized. In doing so, we will provide yet another, more hopeful, story, that the reversible problem may be more to do with the breakdown of dopamine occurring too fast after it has been synthesized, rather than cells dying.
Enzymes
Enzymes are biological catalysts which greatly speed up specific biochemical reactions, e.g. in the human brain and body. Relevant to Parkinson’s Disease is the role of enzymes in the breakdown rates of dopamine. In rare genetic disorders, the body creates not enough or too much of specific enzymes, which can, in turn, result in severe problems due to too little or too much dopamine. However, in folks with PD and other chronic stress conditions, certain enzymes may be insufficiently active or overactive, and hence mimic rare genetic disorders.
The MAo pathway
One way by which dopamine is broken down is via the monoamine oxidase (MAO) enzyme. There are two forms of MAO: MAO-A and MAO-B, with MAO-B being the most relevant one for dopamine. The MAO pathway first breaks down dopamine to a chemical called DOPAL, an aldehyde, plus hydrogen peroxide and ammonia.
DOPAL is in turn is degraded to form another chemical, DOPAC. The breakdown of DOPAL requires the action of another enzyme, called aldehyde dehydrogenase (ALDH). If there is insufficient ALDH, or the MAO-B breaks down dopamine faster than ALDH can keep up, then DOPAL can build up to toxic [to the neurons] levels.
One reason ALDH might not be available is that it may be having to constantly deal with other exposures to other aldehydes. Other sources of aldehydes include: alcohol, certain foods, especially fried foods, perfumes and cosmetics, fungal infections [candida], new carpets and off-gassing from furniture. Exposure to these sources of aldhehdyes should be minimized for folks who are supplementing with endogenous dopamine.
DOPAC is then broken down by another enzyme, COMT, to Homovanillic Acid (HVA), which can then be excreted in the urine. Some studies suggest that HVA levels in the blood may be a proxy for dopamine levels in the brain.
In PD, the MAO pathway may be overactive or there may be too much of the enzyme present, so that dopamine is quickly broken down. MAO seems to increase with age in humans. Importantly for folks with PD, there is also some evidence chronic stress is associated with increased MAO activity, and hence with faster breakdown of dopamine.
Mao Inhibitors
Various pharmaceutical and natural substances can inhibit the action of MAO, with the effect that dopamine stays around longer without being broken down by the MAO parhway. For example, MAO-B inhibitors can be used alongside l-dopa supplementation, with less wear off and longer “on” times for each dose, albeit with the potential for more side-effects.
Rasagiline (Azilect) and Selegiline are examples of pharmaceutical MAO-B inhibitors, while wild green oat extract and the chinese herb Ho Shou Wu/Fo Ti/Polygonum Multiflorum, are examples of naturally occuring MAO-B inhibitors. Apparently, the Ho Shou herb is already used widely in China by people with PD.
Passionflower extract also apparently has some non-selective MAO inhibitor activity. There a few limited studies of its beneficial use for PD but studies not specific to PD also indicate a number of favourable benefits including increased dopamine levels in the brain, as well as sleep and mood improvement.
Licorice root [not the candy] has shown benefits for folks with PD, in part because it also has non-selective MAO inhibitor activity.
Care is needed while taking non-selective MAO inhibitors, which block MAO-A as well MAO-B, together with other medications, and eating cheese [due to the tyramine], which carries the risk of hypertensive crisis, but MAO-B specific inhibitors don’t have this problem.
However, the best, and most natural, way to inhibit excessive MAO-B activity is to reduce chronic stress.