PQQ as a nutritional supplement
History PQQ (Pyrroloquinoline Quinone) was first discovered as the prosthetic group (coenzyme) of enzymes oxidising sugars and alcohols in bacteria. As more enzymes that use PQQ in this way were discovered they become the subject of International Symposia. The first was in 1988. (I organised one in Southampton in 2002, published in Biochim. Biophys. Acta, Vol 1647, 2003).
Enzymes that use PQQ are called quinoproteins. These are analogous to flavoproteins in which riboflavin derivatives take the place of PQQ. Flavoproteins are essential oxidising enzymes in mammals which cannot make riboflavin; this is therefore a vitamin and must be present in the diet. If PQQ-containing enzymes occur in humans then PQQ is likely to be a water soluble B vitamin. However there is no evidence for such enzymes in humans and there is no evidence that PQQ is a vitamin.
Is PQQ a vitamin? In 2003 the Journal Nature published a paper claiming on wrongly interpretated data that PQQ is a new vitamin. This received wide publicity and led to hopeful development of PQQ as a vitamin (by, amongst others) Mitsubishi company. When I pointed out to Nature the completely false foundation (based on misinterpretation of molecular biology databases) they agreed that they must publish a rebuttal both of the molecular biology conclusions (by me) and the nutritional conclusions by Rucker. This led Mitsubishi to market PQQ as a nutritional supplement rather than a vitamin. The story of all this is described at length in my research pages, which include references and downloadable pdfs.
The marketing of PQQ as a nutritional supplement PQQ is now marketed widely as a supplement with claims for a wide range of benefits. These claims are based on many nutritional investigations of PQQ and many studies on the effect of PQQ in isolated cells or tissues or whole experimental animals (mice and rats). The website claims of the marketers are often factually incorrect, wildly exaggerated and have many misunderstandings about biochemistry and physiology.
For unbiased examination of supplements I strongly recommend the website Examine.com which is an "independent organization that presents un-biased research on supplements and nutrition. We currently have over 25000 references to scientific papers". This is an excellent website that examines claims for nutritional supplements and has a lengthy valuable discussion of PQQ.
PQQ and health. Response to an article in Life Extension Magazine Feb 2011
"Generate Fresh Mitochondria with PQQ. Scientists Discover the “Other CoQ10”. By Perry Marcone
Link to the original article
I am writing this response at some length. The same responses are relevant to many PQQ sellers
The article quotes important work by Rucker and colleagues. In early studies, he showed that germ-free mice fed chemically-defined diets thrived more if provided with PQQ. He has been at the forefront of this sort of work and his paper relating PQQ to mitochondrial genesis is the one quoted by the article in Life Extension. We should note that this paper studied the effect of PQQ on isolated cell cultures of mouse liver cells. It requires a lot of extrapolation to conclude that PQQ may have an effect on mitochondrial generation in humans and even more to conclude that PQQ as a nutritional supplement will have an effect on ageing. But of course it may achieve this.
It should be remembered that even if PQQ does have such effects this is not evidence that it has a ‘normal’ role in human physiology – it is probably only acting as a ‘drug’. By its chemical nature it reacts powerfully with free radicals and so is an antioxidant. [Also note that there is no evidence that antioxidants in the diet have any benefit at all].
Some specific comments on the article:
The paragraphs in italics are taken direct from the article, given in the order in which they appeared.
1. The most exciting revelation on PQQ emerged early in 2010, when researchers found it not only protected mitochondria from oxidative damage—it stimulated growth of fresh mitochondria!
This refers to the Rucker study which used liver cells in tissue culture. This is important interesting work but it does not show that dietary supplementation with PQQ in animals/humans will lead to mitochondrial production.
2. Pre-clinical studies reveal that when deprived of dietary PQQ, animals exhibit stunted growth, compromised immunity, impaired reproductive capability, and most importantly, fewer mitochondria in their tissue. Rates of conception, the number of offspring, and survival rates in juvenile animals are also significantly reduced in the absence of PQQ. Introducing PQQ back into the diet reverses these effects, restoring systemic function while simultaneously increasing mitochondrial number and energetic efficiency.
Note that to see these effects animals were often reared in extreme unnatural conditions [that is ok as this was the ‘cleanest’ way of showing effects]. Less effect is likely to be seen in animals if given PQQ in normal conditions. This is not surprising because there is a lot of PQQ in many foods, especially if bacteria have been involved in their production; for example vinegar has a lot of PQQ because it is made using bacteria that use a PQQ quinoprotein to oxidise alcohol to the active component of vinegar – acetic acid.
3. As the primary engines of almost all bioenergy production, the mitochondria rank among the physiological structures most vulnerable to destruction from oxidative damage. PQQ’s formidable free radical–scavenging capacity furnishes the mitochondria with superior antioxidant protection.
Firstly, we should not confuse mitochondrial activity with regeneration [the subject of Rucker’s paper].
Free radicals are inescapable occasional products of reaction with oxygen in the final step in energy production. We have evolved thus far by avoiding damage by these free radicals which are happily mopped up by mitochondrial enzymes with that sole purpose. There is no reason to think that “superior antioxidant protection” is needed.
4. At the core of this capacity is an extraordinary molecular stability. As a bioactive coenzyme, PQQ actively participates in the energy transfer within the mitochondria that supplies the body with most of its bioenergy (like CoQ10).
This is completely untrue. Although it is true that coenzyme Q actively participates in energy transfer within mitochondria, PQQ has not been shown to have any function whatsoever in mitochondria. In bacteria it does have this function. During methanol oxidation for example the first step in energy production is catalysed by a PQQ containing enzyme that is so important that it constitutes 5-10% of the cell’s protein. PQQ enzymes have only been described in bacteria.
5. Unlike other antioxidant compounds, PQQ’s exceptional stability allows it to carry out thousands of these electron transfers without undergoing molecular breakdown. It has been proven especially effective in neutralizing the ubiquitous superoxide and hydroxyl radicals…….. A consistent finding in the scientific literature is that nutrients like PQQ provide more wide-ranging benefits than conventional antioxidants the general public relies on.
As mentioned above, PQQ is a powerful antioxidant and it is stable and so of course will ‘neutralise’ free radicals. But there is no evidence that this ability of PQQ can be relevant to health. There is good evidence that antioxidants in the diet have no positive health benefit and may have slight negative effect. This is published as a Cochrane Review.
6. According to the most recent research, “PQQ is 30 to 5,000 times more efficient in sustaining redox cycling (mitochondrial energy production) . . . than other common [antioxidant compounds], e.g. ascorbic acid.”
This is terrible. Redox cycling is a chemical process that was proposed as a way of measuring PQQ in a test tube. It not relevant in any way to “mitochondrial energy production”.
7. In a revolutionary advance, an essential coenzyme called pyrroloquinoline quinone or PQQ has been shown to induce mitochondrial biogenesis—the growth of new mitochondria in aging cells!
PQQ is not an essential coenzyme in animals [see above]. The studies of PQQ and mitochondrial genesis that stimulated this article were on liver cells in lab culture, NOT ageing cells, or whole animals or humans.
Comments provoked by website of Dr Al Sears
"Vitamin by any other name"
"Those diet dictocrats are at it again… We have strong evidence that there’s a nutrient that really should be classified as a vitamin. Why don’t you know about it and why isn’t it currently called a vitamin? Because they want to make a drug out of it so they can patent it and profit from it"
Really! His website is selling PQQ with claims for all sorts of medical effects. This would not be allowed if it were being marketed as a drug (as nothing has been properly tested or proven). As nutritional supplement he also cannot make his claims on the bottles but he does it on this website. He sells huge numbers of supplements and sells many books.
As with other websites the claims of the marketers are often factually incorrect, wildly exaggerated and have many misunderstandings about biochemistry and physiology.
The questions that must be considered:
Is there any evidence that PQQ is essential in the human diet?
Is the nutritional evidence on lab animals relevant?
Is there any evidence that PQQ has a ‘normal’ role in human metabolism?
To what extent can conclusion based on studies of isolated cells be used as a basis for nutritional supplementation.
There is a huge amount of information about the ‘natural’ role of PQQ in bacterial enzymes.
There is relatively little evidence for PQQ ever having a normal role in biochemistry or physiology of humans.
The concentrations of PQQ measured in humans are tiny.
Studies of rats with a low PQQ diet have a very special diet that contains tiny amounts of residual PQQ that is very much lower than in any normal diet without added PQQ (such as we would typically eat). The rats with added PQQ are given amounts of PQQ that are more than 100 times (g/Kg body mass) that are sold as supplements (typically 20mg).
PQQ is certainly a powerful anti-oxidant because it can remove free radicals. This is ‘merely’ a result of its orthoquinone structure. It does not mean that it has any normal function in this respect.
Mitochondria have their own antioxidant system for removing free radicals that might damage them.
There is no evidence that antioxidants in the diet are a good thing. In fact there is evidence that they may be harmful.
Much of the literature on PQQ as a potential supplement and as being important in normal metabolism is funded by those with a huge commercial interest as suppliers of PQQ (eg Mitsubishi); this is of course does not suggest the science is poorer for this (although the scientists may be richer).
There have been no controlled proper studies on effects (good or bad) of dietary PQQ supplements.
In my judgement
There is no reason to think that PQQ supplements will do good or harm.
Most effects seen in mammalian systems are using PQQ as an experimental ‘drug’ and do not prove that it has any physiological function.
The majority of claims for benefits in PQQ marketing were not made by those publishing the work that is quoted as evidence.