…positive results in animal studies (show) relative avoidance of ischemic reperfusion injury following induced stroke in lab animals. This was due, I understand, to PQQ’s ability to block nitric oxide synthesis. This begs the question; do you think PQQ can cause male erectile dysfunction since normal function depends on adequate levels of nitric oxide?Pyrroloquinoline quinone is a redox active nutrient that can scavenge various reactive oxygen species (ROS), such as superoxide radicals, which can act as deleterious oxidants. This is one of several aspects that make PQQ an effective anti-ischemic agent. PQQ is unable to directly interact with nitric oxide. Research shows it doesn’t block nitric oxide synthesis, which in part addresses the concern about erectile dysfunction. Rather, pyrroloquinoline quinone’s effect on nitric oxide relates to it’s ability to reduce the levels of the major ROS derived from nitric oxide, a compound called peroxynitrite. Nitric oxide can react with superoxide radicals to form the product, peroxynitrite. Peroxynitrite is an oxidant and nitrating agent that can severely damage a wide array of molecules in one’s cells, including DNA and proteins. With respect to PQQ, less peroxynitrite is formed, when the formation of superoxide is blocked or reduced, because of PQQ’s ability to act as an anti-oxidant.
Regrettably, there are no clinical studies that been done to date to directly address whether PQQ is effective in the treatment of Parkinson’s disease, although the assertion is sometimes made in nutritional supplement-oriented blogs and websites less scrupulous than ours. However, there are a number of basic studies that appear promising, which suggest pyrroloquinoline quinone may be beneficial in slowing or altering the progression of Parkinson’s disease.
What is known to date? In studies using experimental animal models, PQQ does interact with the neurotransmitter systems. It appears to be a neuroprotective (also see the post, PQQ, glutamate, nitric oxide and N-methyl-D-aspartic acid receptors). PQQ could potentially protect against neurotoxicity induced by compounds that promote or produce Parkinson-like symptoms in laboratory animals. Moreover, PQQ in chemical assays inhibits the aggregation of alpha-synuclein, a process that is associated with the progression to Parkinson’s disease. Pyrroloquinoline quinone also seems to protect nerve cells by blocking new amyloid beta molecular structures from forming before they can cause cellular damage akin to what is observed in Parkinson’s disease. Although these observations are promising, questions nevertheless remain regarding how direct and specific the actions of PQQ are as they relate to altering the functions of alpha-synuclein and amyloid beta, if and when they are abnormally aggregated.
If you would like to do a deeper dive on this topic you should read:1. Kobayashi, M; Kim, J; Kobayashi, N; Han, S; Nakamura, C; Ikebukuro, K; Sode, K. Pyrroloquinoline quinone (PQQ) prevents fibril formation of alpha-synuclein. 2006 Biochemical and Biophysical Research Communications 349: 1139–44.
2. Zhang JJ; Zhang RF; Meng XK. Protective effect of pyrroloquinoline quinone against Abeta-induced neurotoxicity in human neuroblastoma SH-SY5Y cells. 2009 Neuroscience Letters 464: 165–9.
3. Kim, J; Kobayashi, M; Fukuda, M; Ogasawara, D; Kobayashi, N; Han, S; Nakamura, C; Inada, M et al. Pyrroloquinoline quinone inhibits the fibrillation of amyloid proteins. Prion 4: 26–31.
Does the chemical form of pyrroloquinoline quinone and PQQ salt make a difference for absorption or its biological effects?Many people have noticed that supplement companies are selling products called PQQ but have PQQ salt listed in the ingredients, which is technically a different compound. So it is a thoughtful question to ask “Does the chemical form of PQQ make a difference?” It is a great question and applies to many other compounds commonly found in supplements as well. As usual, there is an important caveat, but the short answer is for the forms of PQQ currently used in supplements, there is probably little difference between the variability of nutritional availability (or relative potency if you will). For example, the organic acid form of PQQ is quickly converted into a salt during the process of digestion (or merely dissolving PQQ into a complex mixture for that matter). The H+ (from the organic acid moieties of pyrroloquinoline quinone) can exchange freely with ionized cations, such as sodium, potassium, magnesium. Both the acid form and salt forms of PQQ, at the intestinal concentrations usually obtained following supplement use, are soluble and probably equally available (absorbable) by the intestine. Animal studies suggest that PQQ is reasonably well absorbed (>50 percent), particularly at low doses (Smidt et al. 1991 Intestinal absorption and tissue distribution of [14C] pyrroloquinoline quinone in mice. Proc Soc Exp Biol Med.197:27-31). It is also worthy of note that ester forms of PQQ have also been studied. Esters are formed when the organic acid moieties in targeted compounds are modified by linking them chemically to an alcohol (methyl, ethyl, or longer carbon-chained alcohol). For pyrroloquinoline quinone, such modifications render or cause PQQ to become less-polar, i.e. less water soluble. In general, these types of modifications are carried out to increase the solubility of the targeted compound in a lipid environment or improve its chemical stability. With regard to digestion and absorption, a portion of the total amount of compound ingested might be absorbed into the body using one of the transport pathways designed for lipid compounds or, alternatively, be converted back to the original staring material by intestinal enzymes and then absorbed. Although there are no data regarding the absorption of PQQ esters, based on what is known about ascorbyl palmitate (an ester form of vitamin C) and tocopheryl acetate (an ester form of vitamin E), it may be assumed that at least a portion of a typical oral dose is absorbed. PQQ in nature exists as free acid, as salts (e.g. the sodium salt of PQQ,) or as a complex derivative of an amino acid, imidazolopyrroloquinoline. The PQQ Ester is a product of chemical synthesis. All of the various forms are absorbed to some degree based on the fact physiological responses result from oral ingestion and supplementation. So what is the caveat? The most important caveat is that most of the PQQ consumed in the diet (even as a supplement) is immediately converted to even more complex derivatized forms than an ester or a salt. PQQ reacts very rapidly with some amino acids, which are found in abundance in food or in the intestine (released because of protein digestion). When pyrroloquinoline quinone is added to aqueous suspensions of experimental diets, the recoveries of “free” PQQ becomes increasing lower in amount with a disappearance of “free” PQQ starting within minutes (Steinberg et al. 2003 PQQ improves growth and reproductive performance in mice fed chemically defined diets. Exp Biol Med (Maywood). 228:160-6). PQQ also forms a compound called imidazolopyrroloquinoline or IPQ (Mitchell et al. 1999 Characterization of pyrroloquinoline quinone amino acid derivatives by electrospray ionization mass spectrometry and detection in human milk. Anal Biochem. 269:317-25). Although one can infer from the Smidt paper linked above that IPQ is absorbed, there are no data for humans or animals that addresses the question of nutritional availability with precision. Right now all we know is that biological effects elicited by PQQ (either in “free” form or as the salt) are observed in animals and humans.
Are there any other vitamin supplements that work well with PQQ?As you are probably aware from reading PQQ, pyrroloquinoline quinone seems to act in promoting mitochondriogenesis and, in a broader context, by protecting neural tissue. Compounds that may promote mitochondriogenesis included resveratrol, quercetin, and hydroxytyrosol (found in olive oil). Other agents that promote mitochondrial function and performance may be synergistic. Such compounds include CoQ10 and carnitine. They either facilitate various metabolic events or aid in moving substrate into and out of the mitochondria. The point here is that just because both PQQ and CoQ10 are quinones, they are doing very different things. One would not want to substitute one for the other. Also, consider the following, consuming a traditionally well-balanced diet (with or without supplements) and regular aggressive exercise is also an excellent formula to stimulate mitochondriogenesis, particularly in muscle. Think of given supplements as a way to potentially optimize this process.
Does lipoic acid function synergistically with PQQ, vitamin C or other antioxidants?Lipoic acid is a cofactor for one of the first steps in a major mitochondrial metabolic pathway. Ascorbic acid plays a number of cellular roles – only a few are specific to mitochondria. As chemicals, they work quite differently in the human body. There are a number of references that one can cite. The following is a good example. (Valdecantos et al. Vitamin C, resveratrol and lipoic acid actions on isolated rat liver mitochondria: all antioxidants but different. Redox Rep. 2010; 15:207-16).
What are some good antioxidants?Many compounds are touted as better or worst regarding there antioxidant potential in chemical assays. In a recent paper, leaders in this field have pointed out that for many types of antioxidants, there effects are due to mechanisms that have little to do with their antioxidant potential (e.g., Hollman et al. The Biological Relevance of Direct Antioxidant Effects of Polyphenols for Cardiovascular Health in Humans Is Not Established. J Nutr. 2011 Mar 30). Although some compounds exert beneficial effects on some biomarkers of cardiovascular health, there is no evidence that this is caused by improvements in their antioxidant capacity. Rather, the real mechanisms have to do with cellular signaling, or the up- or down-regulation of complex metabolic pathways. To use, PQQ as an example, in chemical assays, it is easy to set conditions so that it may function as both a potent pro- and anti-oxidant. What pyrroloquinoline quinone can potentially do is stimulate mitochondriogenesis. The best way a cell has to coordinate oxidative and free radical potential is to optimize cellular organelles, such as mitochondria that are directly involved in oxidative metabolism.
I recently started supplementing with PQQ and have noticed two profound effects. Firstly, a small white, slightly raised area on my lower lip which has been there since I was a teenager (I am now 59) completely disappeared within a week. I find this incredible. Secondly, there has been a significant improvement in my long vision. Previously I had difficulty seeing the letters and digits on car number plates more than three cars in front of me. In fact, at my last appointment with my ophthalmologist late last year I mentioned the deterioration in my sight and she checked my prescription and said it was fine. Now I can see number plates around 6 to 7 car lengths in front of me. John E. – Sydney, Australia
I’m an amateur runner who has struggled for a long time to increase my my VO2 max and aerobic capacity. I have tried different means to make positive strides through both physical training plus changes and augmentation regarding nutrition, with mixed results. The two supplements where I feel like I have gotten the strongest benefit are methoxatin (PQQ) and alpha-lipoic acid. I have as tried rhodiola rosea with mixed results. The three helped in different ways but pyrroloquinoline quinone in isolation seemed to help with recovery allowing me to exert more effort during a subsequent workout, which in theory should help increase the efficiency of adaptation. Mike R. – Berkeley, CA
I have been taking 20 mg of pyrroloquinoline quinone along with 300 mg of ubiquinol daily for about two months. As yet I have not noticed any effects, however I am age 82. Doug G. – Maine
I supplemented my Parkinson’s regimen of Stalevo and Azilect with PQQ and soon felt an increase in nausea and off times. Bob S.
I’ve been consuming pyrroloquinoline quinone along with resveratrol, carthinine and CoQ10. I’ve noticed increased stamina and a drop in blood pressure. It has also made me very calm. I am a 53 yrs old bodybuilder and can work out without getting tired. Mike G. – Tampa Bay, FL
PQQ is amazing! I take 10 milligrams at 8am and also at noon. I benefit from improved mood, concentration, focus, stamina. even my complexion has improved. Georgie – Virginia