If you are worried about PQQ side effects, the good news is the current data for PQQ’s safety is excellent — at least for limited or short-term use (e.g. up to a year) in humans and longer-term use in animals. Long-term (multiple-year) safety in humans still needs to be assessed. However, based on pyrroloquinoline quinone direct to market sales, it may be concluded that hundreds of individuals now take PQQ. Some of these users tend to be aggressive about supplementation (including me), so the chance that an interaction with PQQ may be adverse seems highly unlikely based on the lack of any published reports.
Although there are no direct studies on the potential interaction of PQQ with psychotropic drugs, several studies suggest that the idea is worth exploring. What data that are available regarding cognition are in two animal studies and one human study (see below). The human study is well controlled and the results of the study suggest that PQQ alone or with CoQ10 may be useful for improving higher brain function. Likewise, the animal studies are supportive of this perspective.
To be very clear, not all these supplements and medicines work independently
The best answer about food supplementation and drug interaction is going to come from your personal physician and pharmacist. Although one can identify major mechanisms or even specific functions for given compounds, from a global physiological perspective, there can be cross-talk between the numerous cell-signaling pathways that control cellular function and an enzyme cofactor may interact with numerous enzymes each with a specific function.
Effects of pyrroloquinoline quinone on cell growth and new mitochondria
As a by-product of normal functioning mitochondria will sometimes produce damaging reactive oxygen species (ROS). As we age these ROS degrade our mitochondrial DNA (mtDNA), interfering with the energy production of our cells. When our cells lose their mitochondria, eventually apoptosis or cell death can occur. Most cell’s strategy for mitigating this damage is to turnover mitochondria on a regular basis.
Mitochondria tend to replicate more often than the cells in which they exist. In small animals, this occurs between one and a half to three days in liver cells and two to four weeks in mature brain cells. In general, we want our mitochondria to turnover quickly, the faster the better. In other words, we want to replace our mitochondria before significant mtDNA damage accumulates. Regarding turnover, the best data science has is related to caloric restriction. Studies have shown that calorie restriction speeds mitochondrial turnover (e.g., if calories are not used, less need fo mitochondria). In contrast, when we exercise we tend to slow mitochondrial turnover, which in turn appears to promote mitochondriogenesis. Appreciate, however, that these changes are not that big. A change as little as 5 to15 percent can be dramatic from a normal energy perspective.
So what are the PQQ side effects from withdrawal?
The only data that we have are from animal studies. Giving rats a supplement of pyrroloquinoline quinone that was previously fed diets devoid of PQQ, increases muscle and liver mitochondria about 10 to 20 percent somewhere between half a day to one and a half days. In contrast, methoxatin depletion causes reversal and multiple gene changes in about one to two days.
With regard to humans, there are ways of scaling data from rats to humans. Using those procedures, our best guess is that the withdrawal response in humans from a typical pyrroloquinoline quinone supplement (e.g., 10 milligrams) is somewhat rapid, probably within a week. Assuming circumstances short of starvation, the mitochondrial amounts will return to their relative basal levels. We need to clarify this as “relative basal levels” because the level may depend on the degree to which the respective person is exercising or taking other mitochondria stimulating substances.