Kratom is an herbal product derived from the leaves of Mitragyna speciosa, a tropical evergreen tree indigenous to Southeast Asia. Traditionally, the leaves were chewed by laborers to combat fatigue and improve productivity, and historically, kratom was used in traditional medicine for pain relief and as an opium substitute. Today, it is widely consumed in Western countries as a powder, capsule, or tea, often to self-manage chronic pain or opioid withdrawal symptoms. Its effects come from alkaloids, primarily mitragynine and 7-hydroxymitragynine, which interact with opioid receptors. Growing popularity has led to increased reports of adverse effects, prompting investigation into its connection with potential liver injury.
The Confirmed Link Between Kratom Use and Liver Injury
Kratom consumption has been definitively linked to acute liver injury, known as hepatotoxicity. This adverse reaction is considered a relatively rare and idiosyncratic event, meaning it occurs unpredictably in susceptible individuals. Although not widespread, the number of reported cases has steadily increased as kratom use has become more common.
A review of cases reported to the U.S. Drug-Induced Liver Injury Network (DILIN) found that kratom accounted for a small percentage of herbal and dietary supplement-related liver injuries between 2004 and 2018. Case studies indicate that the onset of liver problems usually begins within one to eight weeks of starting regular use. The pattern of injury is typically mixed or cholestatic, involving impaired bile flow from the liver.
Most long-term users do not experience liver complications, suggesting that general toxicity is not the cause. Instead, the injury appears to be a hypersensitivity reaction dependent on individual biological factors. Medical databases consider kratom a “likely” cause of clinically apparent liver injury, based on the consistency of reported cases. Researchers have confirmed the presence of kratom compounds in the products used by affected patients, strengthening this association.
Recognizing the Signs of Hepatotoxicity
Recognizing the signs of liver distress is important because kratom-induced liver injury can be severe, sometimes requiring hospitalization. Symptoms typically appear after regular use, with a median latency period of 14 to 22 days. The clinical presentation is commonly characterized by cholestasis, involving a reduction or stoppage of bile flow from the liver.
One noticeable sign of liver trouble is jaundice, a yellowish discoloration of the skin and eyes. This occurs when the liver cannot process bilirubin effectively, causing the pigment to build up. Patients often report severe fatigue and nausea as initial complaints.
Changes in bodily waste are common indicators of compromised liver function. Dark urine, often preceding jaundice, is frequently reported. Conversely, stools may become pale or clay-colored due to the lack of bile pigment reaching the intestines. Unexplained and persistent itching (pruritus) is also a frequent symptom associated with cholestasis.
Other signs of liver inflammation include abdominal discomfort or pain, particularly in the upper right side of the abdomen. If symptoms like jaundice, dark urine, or persistent abdominal pain are noticed while using kratom, immediate medical attention is necessary. Although most reported cases result in recovery after cessation, severe cases can lead to significant hepatic dysfunction.
Factors Influencing Risk and Severity
The risk of developing kratom-related liver injury is influenced by several biological and behavioral factors. The proposed mechanism is linked to the metabolism of the active alkaloids, which are broken down by specific liver enzymes like CYP2D6 and CYP3A4. Disruptions to this metabolic pathway can lead to toxicity.
Genetic predisposition plays a significant role in susceptibility to this idiosyncratic reaction. Studies indicate a higher frequency of certain Human Leukocyte Antigen (HLA) alleles, such as HLA-B57:01 or HLA-B44:03, in affected patients. These genetic markers suggest the immune system may be involved, mistakenly targeting liver cells in response to kratom compounds or their metabolites.
Behavioral factors, including the amount and duration of use, directly influence the risk of liver damage. High daily doses and prolonged consumption place a greater metabolic burden on the liver, increasing the likelihood of toxicity. Individuals with pre-existing liver conditions are also more vulnerable to kratom’s negative effects.
Co-ingestion with other substances is a major factor that heightens the risk and severity of liver injury. Combining kratom with alcohol or certain medications—especially those that are liver-toxic or metabolized by the same enzymes—can overwhelm the organ’s processing capacity. Medications that inhibit or induce the CYP450 enzymes involved in kratom metabolism can increase the concentration of toxic compounds, escalating the risk of acute injury.