Enantopure Propylene Glycol ?

[Technocrat]

TOP: L-Propylene Glycol / L-Lactic Acid
BOTTOM: D-Propylene Glycol / D-Lactic Acid
RIGHT: Pyruvic Acid

It bothers me a lot that so many laymen can't perceive stereoisomers as distinctly different substances (especially in biologic systems). I've been doing some research and it seems that metabolism of L/D Propylene Glycol is not the same. D-PG converts to D-Lactic Acid, and L-PG converts to L-Lactic Acid.

While L-Lactic Acid is common to almost all higher animals, the only organisms that create D-Lactic acid are microbes, and each is metabolized by different enzymes and at different rates. In fact if you drink a gallon of (racemic) PG it will be the D-Lactic Acidosis that eventually kills you, while your body easily metabolizes the L-Lactic Acid to Pyruvic Acid.

D-Lactic Acid is not some horrible poison. There are small amounts in some Yogurts, but on the other hand manufacturers stopped putting D-LA into baby formula a long time ago (L-LA is fine). Other than some yogurts only spoiled foods have significant quantities of D-LA

I can't help but wonder if some of the people who have an 'allergy' to PG actually have an allergy to D-PG and/or D-LA. It should be kept in mind that synthetic (normal) PG is always racemic (D/L mixed), while PG created from microbes (which is rare) is usually pure L-PG. This also might explain why some people have allergies to specific brands of e-liquid, and not others. I also wonder if D-PG/L-PG might have different tastes, smells, mouthfeels, throat hits, and lung feelings than racemic PG.

Anyone else know anything about this?

 

[geeker]

No I don't know anything about it, but you have an interesting theory.
d-limonene smells like citrus and l-limonene smells like turpentine. The only difference is their chiral orientation. I take d-limonene as a digestive supplement, but IDK what would happen if someone took l-limonene.

 

[Mister]

Technocrat, I'm a layman but am interested in this. Your thought that considering the stereoisomers of PG as being potentially important to vapers seems to me to be very important.

I've done some searching and the most useful material I've found is at the following link (please add www dot at the start and dot html at the end - I'm not allowed to post links here yet): nature.com/nrneph/journal/v3/n9/full/ncpneph0573, under the heading "Pathophysiology and metabolism of propylene glycol"

Of particular note to my mind are:

"As a result of the stereospecific preference of mammalian alcohol dehydrogenase and aldehyde dehydrogenase for L-propylene glycol, this stereoisomer is cleared most rapidly, and it has been suggested that neurologic dysfunction occurring in propylene glycol toxicity is caused by the accumulation of D-propylene glycol and D-lactate."

"The World Health Organization recommends a maximum dietary propylene glycol intake of 25 mg/kg/day (i.e. 1,875 mg/day for a 75 kg male) The patient described here received an average intravenous propylene glycol dose of 212 g/day (2,827 mg/kg/day)."

The first statement supports your thoughts. Perhaps we'd be best to just be vaping L-PG.

The second statement suggests to me that we are probably a long way from being in trouble as long as we vape just a few ml per day.

But there is much I don't understand on the page at the above link. I'd very much like to hear your take on the information there. (I think that you know much more about this than I do )

 

[Technocrat]

Mister:

Can't see that article because it requires a subscription fee. I might have seen it somewhere else, a lot of sites charge money to see what is free just 3 clicks over. Thanks anyway.

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1. I've done a HUGE amount of research and it's hard to get any concrete facts, most places don't list the stereoisomers as D/L but instead as R/S. I have found ONE site that identifies D/L and R/S together as such:
RACEMIC (CAS 57-55-6)
S = L (CAS 4254-15-3)
R = D (CAS 4254-14-2)

2. Anecdotally this seems consistent, becuase of the (very) few sites that supply S/L or R/D alone there are 3x as many that offer S/L (probably biologically derived). Unfortunately the best price I've found for S/L is $40 (USD)/gram (yikes!) for research grade.

3. I'm not sure if the label for my picture is correct. It seems to correspond to about 75% of the sites I've seen, but so few sites really care about the stereoisomers of PG. Many sites just slap up whichever picture they can find.

4. Nobody mass produces enantopure PG (of either type), because if they did it would only cost about 10%-20% more than normal PG, which is fairly cheap.

5. Propylene Glycol is an intoxicant (CNS depressant/deliriant) just like Ethyl Alcohol, but about 1/3 as potent. This might explain some allergies in people who also have problems with even small amounts of alcohol. It should be noted that the most rabid vaper can only vape about 5 grams (5 ml) per day.

6. Other than Mister's article I couldn't find info about the direct metabolism of D/L-PG so I focused on D/L-Lactate. D-Lactate is converted to pyruvic acid by a similar but distinct enzyme than L-Lactate. If you can't process L-Lactate then you probably didn't even get born, but D-Lactate is sufficiently rare that a person could have a metabolic/enzymatic deficiency and not know it until they ate something with more than trace amounts of D-Lactate precursors.

---

Since this is too obscure for most people let me add something completely different but related, namely 1,3 propane diol. I've seen a lot of places selling this as a 'green' (from fermented corn byproducts) alternative to Propylene Glycol and Ethylene Glycol. Supposedly, according to DOW, it's gentler and more hypoallergenic than PG in cosmetics.

Just for reference:

1,2 hydroxy propane = Propylene Glycol
1,3 hydroxy propane
1,2,3 hydroxy propane = Glycerin

It has only one isomer. I only bring this up because it might be a major contaminant in PG. Many places don't make a distinction between (1,2/1,3)-Propane diol, and technically both can be called Propylene Glycol. On the other hand, it might be a better vaping base than PG and/or have less contaminants. Documentation on it's metabolism is even more obscure than PG. ;(

 

[Mister]

Can't see that article because it requires a subscription fee. I might have seen it somewhere else, a lot of sites charge money to see what is free just 3 clicks over. Thanks anyway.

That's odd, I don't have a subscription and can see that site on two different computers. I'm now able to post links so just to retry, making sure I've got it right here it is: Nature Clinical Practice Nephrology | Acute kidney injury, hyperosmolality and metabolic acidosis associated with lorazepam | Article.

Unfortunately the best price I've found for S/L is $40 (USD)/gram (yikes!) for research grade.

Ouch!

I can think of one company which may have both the resources and the interest to research this subject: Dekang. I've made a post on their thread here.

I only bring this up because it might be a major contaminant in PG. Many places don't make a distinction between (1,2/1,3)-Propane diol, and technically both can be called Propylene Glycol. On the other hand, it might be a better vaping base than PG and/or have less contaminants. Documentation on it's metabolism is even more obscure than PG. ;(

Another very interesting possibility.

Thanks for all your work on this Technocrat!

 

[Technocrat]

The direct link seems to work fine, thanks. That's a very good article. Definitely in my top ten of articles I've seen so far. It summarizes at least 50% of all the (decent) articles I've found so far about Propylene Glycol directly (as opposed to articles that focus more on D/L-Lactate).

Just to put things in perspective, that guy got 1700 grams (ml) of PG over 7 days and had a pre existing problem with liver and kidney damage from chronic alcohol abuse, which further damaged his ability to metabolize PG. That's the perfect storm of PG poisoning (PG overdose + liver damage + kidney damage + more kidney damage from PG overdose).