Comment on HHS-OASH-2026-0232, HHS-OASH-2026-0232-0001, 2026-13608

Fernandes et al. (2019): Kratom-Induced Cholestatic Liver Injury and Its Conservative Management This biopsy-confirmed case report should be considered evidence supporting a 0% allowable 7-hydroxymitragynine (7-OH) threshold rather than a permissible concentration limit. The authors describe a 52-year-old man who developed severe cholestatic drug-induced liver injury after consuming kratom for approximately two months to treat shoulder pain. He consumed approximately 1.5 grams of crushed kratom leaves daily, a quantity consistent with conventional kratom use rather than a concentrated 7-hydroxymitragynine product. His illness resulted in profound jaundice with a peak total bilirubin of 28.9 mg/dL, liver biopsy findings highly suspicious for drug-induced liver injury, and months of clinical follow-up before recovery. After excluding other recognized causes of liver disease, the authors concluded that the findings were consistent with kratom-induced cholestatic liver injury and advised permanent avoidance of kratom and other herbal supplements. Importantly, this publication predates the widespread commercialization of today’s concentrated 7-hydroxymitragynine products. The report contains no evidence that the kratom consumed contained elevated concentrations of 7-hydroxymitragynine or exceeded the proposed 0.05% threshold. Instead, the patient consumed what was described as conventional crushed kratom leaves. This distinction is directly relevant to the current proposal. If the proposed threshold is intended to distinguish products that are considered acceptably safe from those that present unacceptable risk, this case demonstrates that serious, biopsy-confirmed liver injury has occurred following use of conventional kratom without evidence that excessive 7-hydroxymitragynine concentrations were present. The authors also acknowledge an important regulatory concern. They explain that herbal supplements lack strict manufacturing oversight, resulting in variability in chemical composition and increased risk of adverse events. They further conclude that kratom should be avoided until well-designed safety studies are available and call for stricter FDA regulation of herbal supplement manufacturing. Notably, the authors recognize that it remains difficult to determine which specific chemical constituent or contaminant is responsible for liver injury because kratom contains numerous compounds and product composition varies substantially. This uncertainty weighs against permitting any measurable amount of an opioid-active alkaloid through a concentration-based exemption. Accordingly, this case report does not support the conclusion that kratom products containing less than 0.05% 7-hydroxymitragynine are inherently safe. Instead, it demonstrates that clinically significant toxicity has been documented in a consumer using conventional kratom, with no evidence that elevated 7-hydroxymitragynine concentrations were present. For these reasons, this case report should be considered evidence supporting a 0% allowable 7-hydroxymitragynine standard. A zero-tolerance standard provides a clearer, more protective, and more readily enforceable public health approach than allowing a measurable concentration of a pharmacologically active opioid agonist in products marketed as kratom.