Unanswered Palmitoylethanolamide may soon to be a prescription drug

[stimtron]

Looks like it's nearing the approval process while I'm hopeful they won't pull it off the market otc I don't see what would stop them. Just a heads up.

https://www.apnews.com/Business Wire/cfa4788469924eb5a885d61d110b4ca3

 

[Jeremyk1]

That article is mostly just about the company being bought. That said, it seems what they’re using for their “drug” is micro-PEA, so I don’t think it’ll interfere with supplements. But you probably won’t be able to find micronized PEA, if that’s even a thing. I can’t say for sure though, just a guess.

 

[HIT4ME]

My understanding of this is that it has horrific bioavailability. Do you know anything on that? Is this incorrect?

 

[stimtron]

That article is mostly just about the company being bought. That said, it seems what they’re using for their “drug” is micro-PEA, so I don’t think it’ll interfere with supplements. But you probably won’t be able to find micronized PEA, if that’s even a thing. I can’t say for sure though, just a guess.

Yes but the key part is a drug company put an NDI to get PEA approved as a drug. Last time a company did this with a natural form of B-6 called pyridoxamine they made the FDA take all natural brands otc off the market. I don't see why they wouldn't do the same here. Under the DSHEA if a drug company files an NDA before it's sold as a supplement it's considered a drug and not a supplement.

 

[VaughnTrue]

Yes but the key part is a drug company put an NDA to get PEA approved as a drug. Last time a company did this with a natural form of B-6 called pyridoxamine they made the FDA take all natural brands otc off the market. I don't see why they wouldn't do the same here. Under the DSHEA if a drug company files an NDA before it's sold as a supplement it's considered a drug and not a supplement.

*NDI

You can still buy pyridoxamine over the counter, available from countless brands.

The same will be true for PEA in this instance. Supplement companies won't be able to make disease state claims but it should still be available in the same way it has been for years

 

[stimtron]

*NDI

You can still buy pyridoxamine over the counter, available from countless brands.

The same will be true for PEA in this instance. Supplement companies won't be able to make disease state claims but it should still be available in the same way it has been for years

I did a google search and came up with nothing but you're saying countless brands make it? Can you name one? I'd like to take it for antiaging purposes if I can get my hands on it the studies looked very promising.

The FDA officially banned it for sell as a dietary supplement like DMAA and pulled several off the market years ago. I guess companies could still sell it but would be in violation of FDA rules.

http://emord.com/blawg/the-pyridoxamine-trap/

"FDA agreed with Biostratum. In 2009, FDA took the extraordinary step of declaring that all products containing pyridoxamine are not dietary supplements. In reaching its decision, FDA rejected comments from industry that it was marketed as a dietary supplement prior to October 15, 1994. For example, FDA ignored comments stating that the ingredient was included on dietary supplement industry lists of grandfathered ingredients because the comments did not include documentation of marketing, such as catalogs, from the relevant time period. "

Looks like one company is trying to get the FDA to allow sales but no new developments since then.

https://www.naturalproductsinsider.com/regulatory/fda-petition-implicates-interests-dietary-supplement-pharmaceutical-industries

 

[stimtron]

My understanding of this is that it has horrific bioavailability. Do you know anything on that? Is this incorrect?

I heard the same I was using LEF's but I switched to Levagen+ it's supposed to have 2x the bio due to some lipid matrix. Seems that or micronized is the best way to go but micro is $$$.

 

[HIT4ME]

Interesting - so I have a grandmother who is on warfarin and takes pain medications, etc. There has been discussion about using CBD and even cannabis itself to treat her pain. I cannot allow it because of case studies that show cannabinoid metabolism potentially leads to deadly elevated INR rates when combined with warfarin.

I was curious about this, and it turns out PEA actually causes an increase in prothrombin and may actually cause blood clots. An analog has been noted to be elevated in acute stroke victims as well. It would appear the liver CYP450 functions between many cannabinoids and warfarin are the same, but cannabinoids themselves actually help blood clotting. The elevated stroke in pot smokers looks controversial and based on many statistical studies, which are notoriously flawed - but these other studies seem to at least provide a supporting pathway. From what I can see though, in people without other risk factors, these studies seem to indicate that clotting is not elevated outside of normal ranges (suggesting there has to be other factors for it to be an issue).

 

[stimtron]

Interesting - so I have a grandmother who is on warfarin and takes pain medications, etc. There has been discussion about using CBD and even cannabis itself to treat her pain. I cannot allow it because of case studies that show cannabinoid metabolism potentially leads to deadly elevated INR rates when combined with warfarin.

I was curious about this, and it turns out PEA actually causes an increase in prothrombin and may actually cause blood clots. An analog has been noted to be elevated in acute stroke victims as well. It would appear the liver CYP450 functions between many cannabinoids and warfarin are the same, but cannabinoids themselves actually help blood clotting. The elevated stroke in pot smokers looks controversial and based on many statistical studies, which are notoriously flawed - but these other studies seem to at least provide a supporting pathway. From what I can see though, in people without other risk factors, these studies seem to indicate that clotting is not elevated outside of normal ranges (suggesting there has to be other factors for it to be an issue).

Cannabis cannabinoids have been implicated as counterained with warfarin use yes but I've seen nothing in the studies with PEA regarding any serious side effects or increased risk of blood clots which is already in my body and don't act strongly on CB1 and CB2 that cannabis does.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5332261/

Food Sci Nutr. 2017 Mar; 5(2): 292–309.
Safety of micronized palmitoylethanolamide (microPEA): lack of toxicity and genotoxic potential

A common observation from the totality of the evidence described is the lack of adverse effects of doses as high as 1200 mg of microPEA per day. The most common regimen was 300 mg twice a day, although a sizeable body of evidence is accumulating on amounts 1200 mg/day. Adverse effects have been reported to be absent (Gatti et al. 2012; Skaper et al. 2014; Paladini et al. 2016).

Where did you read it caused blood clots?

 

[stimtron]

Interesting - so I have a grandmother who is on warfarin and takes pain medications, etc. There has been discussion about using CBD and even cannabis itself to treat her pain. I cannot allow it because of case studies that show cannabinoid metabolism potentially leads to deadly elevated INR rates when combined with warfarin.

I was curious about this, and it turns out PEA actually causes an increase in prothrombin and may actually cause blood clots. An analog has been noted to be elevated in acute stroke victims as well. It would appear the liver CYP450 functions between many cannabinoids and warfarin are the same, but cannabinoids themselves actually help blood clotting. The elevated stroke in pot smokers looks controversial and based on many statistical studies, which are notoriously flawed - but these other studies seem to at least provide a supporting pathway. From what I can see though, in people without other risk factors, these studies seem to indicate that clotting is not elevated outside of normal ranges (suggesting there has to be other factors for it to be an issue).

Cannabis cannabinoids have been implicated as counterained with warfarin use yes but I've seen nothing in the studies with PEA regarding any serious side effects or increased risk of blood clots which is already in my body and don't act strongly on CB1 and CB2 that cannabis does.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5332261/

Food Sci Nutr. 2017 Mar; 5(2): 292–309.
Safety of micronized palmitoylethanolamide (microPEA): lack of toxicity and genotoxic potential

A common observation from the totality of the evidence described is the lack of adverse effects of doses as high as 1200 mg of microPEA per day. The most common regimen was 300 mg twice a day, although a sizeable body of evidence is accumulating on amounts 1200 mg/day. Adverse effects have been reported to be absent (Gatti et al. 2012; Skaper et al. 2014; Paladini et al. 2016).

Where did you read PEA itself caused blood clots? Which analog and how did it function differently? It's been in clinical use in Europe for decades without any reported issues.

 

[HIT4ME]

Let me see if I can re-find it - it didn't seem to increase clotting outside of the normal range from what I can tell. It suggests to me that it plays a role in clotting that we are not aware of, part of the cascade - and for most people probably has no issue at all, but may have an issue if you have other factors that may lend to stroke. Just a hypothesis...hard to say from one study too; the evidence is weak. It seems like we have statistical evidence (which is often flawed) and now this at least suggests a pathology but would certainly need more study.

 

[HIT4ME]

Here is one of them, I think I saw a second - again, not exactly a smoking gun, just something interesting. And of course, clotting itself isn't bad. Too much or too little is. I think it's probably something where there is a much bigger picture where these chemicals are needed for proper clotting and when things go wrong, they may have a role.

For instance, another issue is that when people go on warfarin they often stop eating greens, etc. (or never did to begin with) and these veggies are often sources of chemicals like quercetin which help avoid blood clotting. So we tell people to take warfarin and avoid these foods because of vitamin K, but in the process they also avoid the natural blood thinners that may have been lacking to begin with.

It all makes your head spin after a while.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3984601/

 

[HIT4ME]

Oh, and they found that AEA is often elevated in acute stroke victims. This is not cause/effect and it could be that AEA is protective, or it could be that it triggers something. We just don't know I guess.

Like you said, there is a lot of use that suggests no issues at all....so it may just be academic.

 

[stimtron]

Let me see if I can re-find it - it didn't seem to increase clotting outside of the normal range from what I can tell. It suggests to me that it plays a role in clotting that we are not aware of, part of the cascade - and for most people probably has no issue at all, but may have an issue if you have other factors that may lend to stroke. Just a hypothesis...hard to say from one study too; the evidence is weak. It seems like we have statistical evidence (which is often flawed) and now this at least suggests a pathology but would certainly need more study.

I haven't seen anything on PEA and clotting pro or con it seems pretty neutral and been around since the 60's not that we know all potential side effects but I'd like to think most of them by that period of being regularly prescribed. I know vitamin K supports clotting but also reduces calcification builds which can otherwise cause heart problems down the line. If you're at risk for stroke or heart attacks you should consider all the factors involved. So many people on warfarin end up with worsening heart conditions by increasing their arterial calcification.

 

[stimtron]

Oh, and they found that AEA is often elevated in acute stroke victims. This is not cause/effect and it could be that AEA is protective, or it could be that it triggers something. We just don't know I guess.

Like you said, there is a lot of use that suggests no issues at all....so it may just be academic.

It seems to function as a biomodifier as a responder to inflammation or damage since when given to stroke victims it improves their symptoms.

https://www.ncbi.nlm.nih.gov/pubmed/26706245

" In the second arm, a cohort of 250 stroke patients undergoing neurorehabilitation on either an inpatient or outpatient basis were treated for 60 days with a pharmaceutical preparation of co-ultraPEALut (Glialia). At baseline and after 30 days of treatment, all patients underwent a battery of evaluations to assess neurological status, impairment of cognitive abilities, the degree of spasticity, pain, and independence in daily living activities. All indices showed statistically significant gains at study end. Despite its observational nature, this represents the first description of co-ultraPEALut administration to human stroke patients and clinical improvement not otherwise expected from spontaneous recovery. Further, controlled trials are warranted to confirm the utility of co-ultraPEALut to improve clinical outcome in human stroke. "