Does the chemical form of pyrroloquinoline quinone and PQQ disodium salt make a difference for absorption and its biological effects?
Many people have noticed that supplement companies are selling products called PQQ but have PQQ disodium 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 in addition to PQQ disodium salt, ester forms of pyrroloquinoline quinone 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 starting 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 a 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 what we know is that many of the reported biological effects elicited by PQQ supplementation (either in its “free” form or as it is marketed as “PQQ disodium salt”) are observed in both animals and humans.