Comment · Mon, April 25, 2022 · Nootropics Depot & Natrium Health
Tongkat Ali has the potential to induce DNA damage
What they were answering
educateddrugdealer42 · 1 points
As mentioned, DNA damage requires extra caution. But yeah, which safety factor one decides to use is not written in stone, and the EFSA is being extremely cautious..
u/MisterYouAreSoDumb · Nootropics Depot & Natrium Health
The thing is that they didn't find totoxicity at the lower doses.
While the positive results observed at the highest dose of the NF tested (2,500lg/mL) may have been caused by cytotoxicity, no signs of overt cytotoxicity were seen at the low- and mid-dose group (500 and 1,000lg/mL).
You can't just take the highest dose (the only one that found any toxicity) then apply a correction factor to bring it back down to reasonable dose levels, when you have direct data on lower doses not causing the toxicity. If reasonable doses had that effect, they would have saw that effect in the study. Their wording makes it sound like they are saying it is not safe at any level. Normal people will read that and think they said it was just not safe. However, what they are actually saying is that there is a level at which it might cause damage, so you can't just dose as high as you want. They should say: "The Panel concludes that the safety of the NF has not been established under EVERY condition of use." It's also literally just one in-vitro test for which they cannot determine the cause, and since it is already shown not to be cytotoxic at lower doses, they make a jump to conclusion that it must be genotoxic. Imagine if pharmaceutical toxicity studies were run this way... Let's give rats amphetamine at 2,000mg/kg and see if we see damage. Damn, they died! I guess it's not safe at any dose. Toxicity studies in pharma are way more controlled and relevant to the doses that will be used in humans. I suppose the argument will be: "Well this is more serious, because it is a genotoxic effect." Well that was a postulation made by them, not an actual finding. Also, amphetamine can cause genotoxicity.
http://insight.jci.org/articles/view/90427/files/pdf
That's actually a human study, too. So do we pull Adderall from the market now? Let's just look at one thing they mentioned in the study: coumarin. They found small levels of coumarin in tongkat. Coumarin is also found in higher amounts in cinnamon. Well coumarin can be genotoxic.
https://oehha.ca.gov/media/downloads/crnr/coumarinhid.pdf
It's the dose that makes the poison. This is why we come up with MADLs. If we just upped the dose on everything to ridiculous amounts, then said that anything we found toxicity with at any dose was unsafe, we would have to pull a lot of shit from the market. Also, to be clear, they did NOT conclusively find genotoxicity with Tongkat Ali. They postulated that was what they found.
No degenerative changes were seen in the duodenum of any animal. ThePanel notes that the aetiology of the hedgehog cells is still unclear and that scientific literature indicates that their formation can be due to cytotoxicity, but also to genotoxicity or apoptosis (OECD TG 489). Since the NF administered at the dose of 2,000 mg/kg bw per day led to the marked increase in %TI without being associated with signs of cytotoxicity or cell death in the stomach and duodenal tissues in the main experiment and no histological damage in the duodenal tissue was observed in the follow-up experiment (for which association with comet positive cells was not performed), the Panel concludes that the DNA damage was due to a genotoxic effect of the NF rather than primarily to controlled DNA fragmentation (apoptosis) or unspecific general cell toxicity.
So this is not even conclusive findings yet, and followup studies need to be ran to confirm if it is even an issue at those absurdly high doses.