Comment · Thu, March 10, 2022 · Natrium Health & Nootropics Depot
The Nutritional Supplement Alpha-GPC Promotes Atherosclerosis [2021]
What they were answering
Regenine · 54 points
I don't mean to be rude, but if you criticize the author based on their conflict of interest, you might as well remind people you are the owner of a company which sells Alpha-GPC (Nootropics Depot). Don't you also have a conflict of interest defending Alpha-GPC?
Anyway, the link between TMAO and atherosclerosis extends far beyond the scope of this paper. It's not just in vitro - TMAO is associated with incident thrombotic risk in humans (heart attacks and strokes), and TMAO directly promotes thrombosis in rodents, as is evident by protection from thrombosis when feeding choline together with an antibiotic (which kills the bacteria that produce TMAO):
Gut Microbial Metabolite TMAO Enhances Platelet Hyperreactivity and Thrombosis Risk
https://www.cell.com/cell/fulltext/S0092-8674(16)30113-1
Plasma TMAO levels in subjects (n > 4,000) independently predicted incident (3 years) thrombosis (heart attack, stroke) risk.
Choline Bitartrate supplementation in humans is pro-thrombotic, increases risk of blood clots by increasing platelet aggregation (platelets become more "sticky"):
Gut Microbe-Generated TMAO from Dietary Choline Is Prothrombotic in Subjects
https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC5460631/
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All in all, this paper is far from the only evidence of the problematic nature of TMAO. The 2 papers I have added in this comment have no conflicts of int…
u/MisterYouAreSoDumb · Natrium Health & Nootropics Depot
Am I writing research papers making bold claims about it? Do I own patents and have exclusive rights to sell alpha-GPC? Do I own patents for the methods used to measure things in said research papers? Obviously the situation is very different. Am I biased? You're damn right I am biased. I think anyone that has even taken alpha-GPC before would be somewhat biased. I think anyone here on this forum right now is biased, if they are perfectly honest with themselves. However, it's nowhere near the conflict of interest of the author of this study. I am also responding to the article being posted, not actively going around and spreading information about it. I also clearly said that I was not claiming that their data was for sure bad. I said I would need to get into the data more to have a solid opinion on it.
Now I am not saying their data is fraudulent or wrong. I need to dig more into the science to have a solid opinion of that.
I also had not seen this was posted on here a few weeks ago. Someone linked it to me via PM after this post.
https://www.reddit.com/r/Nootropics/comments/swjyig/the_nutritional_supplement_lalpha/
/u/cynthesistoday gave some good responses on there. Could he have a conflict of interest, and be some shady figure behind a cabal of alpha-GPC producers? I guess maybe...
Every time someone measures their TMAO, two of the authors of this paper get a royalty.
If you read papers where Cleveland Clinic researchers are _not_ authors, you will see much, much less certainty in the consideration of cause, effect or simple bystander status of TMAO and sources of choline or carnitine. One recent review:
https://sci-hub.se/https://doi.org/10.1007/s11883-021-00910-x "Trimethylamine N-Oxide (TMAO), Diet and Cardiovascular Disease" (2021) Includes studies of different food and supplement intakes of choline and carnitine sources.
My findings were the same as him. The author Hazan literally owns the patent for measuring TMAO. So even someone trying to replicate this author's findings would have to use his patented process to do it. You don't see the massive conflict there?!?
There are 68 hits in the full article for the search term "TMAO". The mice in this study were APOE-/- mice. They deliberately destroyed a native lipid transport mechanism to cause the mice to be particularly prone to atherosclerosis. It is an "accepted model for atherosclerosis" but not all things that affect this model affect standard biology. APOE does many other things whose results they did not measure or control for. They did not provide co-factors for alternate pathways for processing choline. They did not measure homocysteine levels. Homocysteine is a significant effector of atherosclerosis and a major pathway for processing choline via the PEMT pathway.
I stand by my downgrading of papers with Hazan as co-author. 16S rRNA is a very flawed measurement method. The anti-inflammatory, pro-inflammatory and pro-resolving immune space is extremely complex.
He brings up good points. Also, as I said before, I personally need to do more research to have a solid stance on it myself. It's kind of hard to write off my concern over these massive conflicts just because I also sell some alpha-GPC. If I had the exclusive patent for alpha-GPC, and owned the patent for measuring the effectiveness of alpha-GPC, then maybe the equivalence would be warranted. However, I would have brought up the same conflict issues had I been some rando bus driver reading this study. The conflicts are conflicts, regardless of who brings them up. And if alpha-GPC proves to be harmful, so be it. I care about the truth. I'll drop alpha-GPC tomorrow if I need to. It's really not a big part of our sales, and I don't really have a horse in this race. However, these are pretty big claims by someone with a massive conflict in both the scientific methodology aspect of the research, but also drug alternatives to the findings of the research. If you think that's the same as some dude on Reddit who sells alpha-GPC amongst hundreds of other products, I don't really know what to tell you. But again, maybe the risk link is there. Maybe it is something that needs to be addressed and looked into further. I will have to research more to finalize my personal stance on it.