A hepatotoxicity warning was triggered by EFSA at doses of 800 mg EGCG per day or more for supplementation, as indicated by increased levels of serum transaminases observed in interventional studies. Commission Regulation (EU) 2022/2340 introduced green tea extracts with EGCG into Annex III to Regulation (EC) 1925/2006: a daily serving should have less than 800 mg of EGCG; the product label should list the amount of EGCG in each serving and the maximal number of servings per day; and there must be four warnings required: for daily limit, simultaneous use of green tea preparations, pregnancy, lactation and minors under 18 years old, and consumption without food. Traditionally prepared infusions are outside scope. Degalloylated and low-EGCG extracts are the compliant reformulation route.

FDA has concluded that NAC is not included in the definition of dietary supplements since it was approved as a drug before marketing as a supplement. FDA adopted its enforcement discretion approach in August 2022 and has shown willingness for rulemaking, although as of the status date, it has not yet proposed a rule, and the exclusion still stands. A product relying on NAC in its US detoxification formula is relying on discretion rather than rights and should have a documented contingency reformulation strategy, usually consisting of cysteine donor replacement together with glycine and selenium to maintain the rationale of glutathione support.

Neither substance is present on the EU Union list of novel foods authorized by Regulation (EU) No 2015/2283. Any EU launch requires the determination of status through Article 4 consultation with the competent authority of a member state; in case of novelty, the application process starts, which is a multi-year process. US dietary-ingredient status and NDI notification history should be documented before the design of the ingredient.

Absorption is non-selective. Activated charcoal in combination with vitamins, plant extracts or probiotics destroys the very product that is being combined with. In turn, people using oral drugs, which can be contraceptive pills, run the risk of having a drug interaction. An authorized EU health claim concerns the reduction of excessive flatulence after meals at a specific dosage regimen. It should be noted that there is no claim on toxin removal. FRL will formulate charcoal products, but only as standalone SKUs carrying explicit separation-of-dosing guidance on pack.

Curcumin formulations with high bioavailability have been associated with idiosyncratic liver toxicity, which was significantly correlated with the HLA-B*35:01 genotype: in the US DILIN study, among ten cases, seven were carriers of the allele with a frequency in the control population around 0.06, and three out of seven products under chemical analysis also contained piperine [13]. Apart from this, there is another concern about this group of products: one of the mechanisms for increased exposure to curcumin due to piperine is inhibition of UGT-mediated glucuronidation. Phase II inhibitor seems to be a strange addition to a product designed for Phase II support. Phospholipid complex, cyclodextrin or colloidal dispersion strategies can provide exposure increase without drawbacks mentioned above.

Statements that a product removes, chelates or eliminates heavy metals or environmental toxins are treatment claims for a toxicological condition. They place the product in drug territory in every major market and have been a durable enforcement priority for FDA and FTC. This wording does not appear in FRL-developed copy.