11 replies to this topic

[normalizing]

The European Food Safety Authority (EFSA) has taken the reins in the safety evaluation of Mitsubishi’s novel antioxidant salt ingredient following member state toxicity concerns.; http://www.nutraingr...-state-concerns

[Turnbuckle]

Here are the concerns--

 

10. The Irish assessment concludes that insufficient data has been provided to

support the product’s safety. In particular uncertainties remained in relation to

whether the compound is genotoxic as a result of weak positive reactions in the

chromosome aberration test but negative results in vivo. The applicant has agreed

that the supplement containing PQQ would not be recommended for use by children

or pregnant women.

 

11. At high doses in the animal studies adverse effects including crystallisation of

PQQ in the urine and renal toxicity were seen as well as dark green coloured faeces.

The opinion suggests that if the NOAEL identified in rats of 100mg PQQ/Kg bw day

was accepted the proposed dose would have a margin of safety of 143. At the dose

identified as the NOAEL crystallisation of the material in the urine was seen along

with the presence of protein positive reactions. The opinion notes that the

toxicological data and human data are insufficient to draw conclusion on the risks

associated with long term consumption at the proposed dose. 

https://acnfp.food.g...t/files/pqq.pdf

 

 

Not much at all, but the manufacturer is not well enough connected with the regulators.

[normalizing]

The opinion notes that the

toxicological data and human data are insufficient to draw conclusion on the risks

associated with long term consumption at the proposed dose

 

in my view, i rather stay away from it until this is ultimately resolved. i kind of feel bad using PQQ high doses in the past as i have not noticed any benefits but i assume combination of other things, did cause me side effects

[niner]

The effects seen in rats were typical of megadoses of many compounds.  The rats were given 100 mg/kg/d.  The human equivalent dose for a 70 kg subject would be 1167 mg/day.  (this HED uses a scaling factor of 6.  Without scaling, the dose would be 7 grams/day in a 70 kg person.)

 

From the committee paper:
 

At high doses in the animal studies adverse effects including crystallisation of PQQ in the urine and renal toxicity were seen as well as dark green coloured faeces.
The opinion suggests that if the NOAEL identified in rats of 100mg PQQ/Kg bw day was accepted the proposed dose would have a margin of safety of 143. At the dose
identified as the NOAEL crystallisation of the material in the urine was seen along with the presence of protein positive reactions. The opinion notes that the toxicological data and human data are
insufficient to draw conclusion on the risks associated with long term consumption at the proposed dose.

[normalizing]

whats the point of testing for toxicity in such high doses? obviously i can tell you without doing research on this that megadoses will cause some detrimental effects. so stupid!

[airplanepeanuts]

According to this paper

 

https://www.ncbi.nlm.../pubmed/2546903

 

11.5 mg/kg in rats caused some kind of Nephrotoxicity.

 

For a 70 kg human this amounts to about 100mg, if I am not mistaken.

 

This does seem  close to the typical 20mg..

[Oakman]

According to this paper

 

https://www.ncbi.nlm.../pubmed/2546903

 

11.5 mg/kg in rats caused some kind of Nephrotoxicity.

 

For a 70 kg human this amounts to about 100mg, if I am not mistaken.

 

This does seem  close to the typical 20mg..

 

Just been reading up on HEDs for another reason and for example, and according to this allometric scaling calculator: http://clymer.alterv.../allometry.html

 

Weight 1 > 0.15kg

Weight 2 > 70kg

Dose 1 > 1.72mg

Exponent > .074

 

Dose 2 > 163.347 mg

Ratio 1 > 11.533 mg/kg

Ratio 2 > 2.334 mg/kg

 

If that's correct, then the HED is 163mg based on 11.5mg rat dosage. Taking 10 to 1 safety margin would be 16.3mg dose, close to the typical 20mg sold. Does not sound unreasonable. Is this calculation incorrect?

[normalizing]

dear lord, its so complicated to translate doses from rats to humans and still not any easier way available out there? this has been going on for years on this forum and it seems people still dont get the doses right

[Oakman]

dear lord, its so complicated to translate doses from rats to humans and still not any easier way available out there? this has been going on for years on this forum and it seems people still dont get the doses right

Of course it appears difficult, but there seem to be standard methods of calculating oral dosing that are used in human trials based on the doses given to animals in original studies. I've checked multiple sources and references and the calculators online givesimilar, if not identical results. Then, from those the 1/10th dose is what is given to humans in studies to provide a generous margin of safety.

 

 There are other algorithms, of course, for example, when oral dosing is not used. And as you say, there is only conjecture and experimental experience, not solid scientific evidence that all this stuff is correct in every situation, because of the many variables between the original test animals, bioavailability, human gut absorption variables, and compound method of action in the human body, etc, etc. Nevertheless, not too many people are apparently adversely affected using these methods, I guess that's why they are used.

 

For myself, I was trying to figure dosing for a relatively uncommon supplement I've started taking, based on available studies (with results I wanted) being conducted, so I got interested in how to convert them to HEDing.  Fun stuff, and now I know! Such fun to run personal N=1 studies!

[niner]

 

According to this paper

 

https://www.ncbi.nlm.../pubmed/2546903

 

11.5 mg/kg in rats caused some kind of Nephrotoxicity.

 

For a 70 kg human this amounts to about 100mg, if I am not mistaken.

 

This does seem  close to the typical 20mg..

 

Just been reading up on HEDs for another reason and for example, and according to this allometric scaling calculator: http://clymer.alterv.../allometry.html

 

Weight 1 > 0.15kg

Weight 2 > 70kg

Dose 1 > 1.72mg

Exponent > .074

 

Dose 2 > 163.347 mg

Ratio 1 > 11.533 mg/kg

Ratio 2 > 2.334 mg/kg

 

If that's correct, then the HED is 163mg based on 11.5mg rat dosage. Taking 10 to 1 safety margin would be 16.3mg dose, close to the typical 20mg sold. Does not sound unreasonable. Is this calculation incorrect?

 

 

150 grams is pretty light for a rat.  I used 300 grams, giving dose1 = 3.45 mg.  I used the default exponent of 0.75.  (is your 0.074 a typo?)  With these settings, I got 206 mg as the 70kg human equivalent dose.  There's another consideration though--  The rats in this paper were dosed intraperitoneally.  That will typically result in a much higher plasma concentration than an oral dose, possibly as much as a factor of 10, depending on the drug.  I think PQQ is probably fine for humans at a dose of 20 mg, but I wouldn't megadose it, and it might be a good idea to use one of the lower dose versions.  Jarrow has one that's 10 mg, for example.
 

Edited by niner, 26 October 2016 - 09:59 PM.

[normalizing]

uhm a question, why use it at all? does it have any vital study behind it that it does help tremendously in some biological department?

[Oakman]

uhm a question, why use it at all? does it have any vital study behind it that it does help tremendously in some biological department?

 

Examine.com's opinion of PQQ is fairly modest, and they seem to dismiss "mitochondrial biogenesis" as anything notable >

 

https://examine.com/...noline-quinone/

 

"It holds a potential to modify signalling in humans, and although the oxidation in the blood (easiest thing to measure) in mostly unaffected it also retains the potential to act as an intracellular antioxidant. The enhancement of mitochondrial function may also occur, but beyond some alterations in signalling and the mitochondrial biogenesis most other properties of PQQ are unlikely to extend to humans"

 

Others are more optimistic regarding on-going studies of PQQ and its possible benefits >  http://doctormurray....ient-superstar/

 

"PQQ supplementation resulted in significant decreases in the levels of the inflammatory markers of plasma C-reactive protein and IL-6. Furthermore, the changes in urinary metabolites consistent with enhanced mitochondria-related functions. The data are among the first to link systemic effects of PQQ in animals to corresponding effects in humans."

 

And, interestingly, they give dosing advice which was the recent discussion, and rationale:

"What is the proper dosage? One question regarding PQQ is what is an effective dosage? Specifically, if the nutritional requirement of PQQ is likely less than 500 mcg daily why is the recommended dosage 10 to 20 mg? In order to get a measured response in mitochondrial function in adult animals there is the need to feed higher amounts of PQQ much like why only 8 to 15 mg of vitamin C might protect against the overt signs of scurvy, the recommended dietary allowance currently stands at 75 to 90 milligram per day (for adults, excluding pregnant and lactating women) for optimal function, and even higher amounts are required for clinical applications.The current recommendation of 10 to 20 mg of PQQ daily is based upon the equivalent dose in animals has consistently improved various mitochondrial functions. There are also some clinical and observational studies that justify the dosage, especially the 20 mg dosage for enhancing memory."

My overall take from these and other opinions is that PQQ is likely useful, yet to be fully evaluated as to the extent of its benefits, and likely more beneficial in older individuals. And, similar to many substances we have heard about in the last few years, it holds promise. As with anyone's N=1 experiments, it's available, appears to be safe at moderate dosing, and so at the user's discretion as to use or not.

Edited by Oakman, 27 October 2016 - 03:24 PM.