What are the proven supplements for preventing or treating hepatotoxicity (liver damage)?

From the Guidelines

N-acetylcysteine (NAC) is the most proven supplement for hepatotoxicity, particularly in cases of acetaminophen overdose, and should be administered to patients with suspected or known acetaminophen overdose and hepatotoxicity. The use of NAC in patients with hepatotoxicity due to acetaminophen overdose is supported by several studies, including a prospective Class II study by Keays et al. 1 that found a 28% absolute reduction in mortality with NAC use. Another Class III study by Harrison et al. 1 also demonstrated a 21% reduction in mortality with NAC use in patients with hepatic failure due to acetaminophen toxicity.

The management of acetaminophen hepatotoxicity is also discussed in the AASLD position paper on the management of acute liver failure 1, which recommends drawing acetaminophen levels in all patients presenting with acute liver failure and considering NAC administration if acetaminophen ingestion is known or suspected.

While other supplements such as vitamin E may have antioxidant and anti-inflammatory effects, the evidence for their use in hepatotoxicity is not as strong as it is for NAC. For example, a study on the use of vitamin E in nonalcoholic fatty liver disease found that high-dose vitamin E (800 IU/day) improved liver histology, but also carried safety concerns due to the increased risk of prostate cancer or hemorrhagic stroke 1.

In terms of dosage, NAC is typically administered at a dose of 600-1200mg daily, although the exact dosage may vary depending on the specific clinical scenario. It is essential to consult a healthcare provider before starting any supplement regimen, especially if you have existing liver disease or take medications.

Some key points to consider when using NAC for hepatotoxicity include:

• NAC should be administered as soon as possible after acetaminophen overdose
• The dosage and duration of NAC treatment may vary depending on the severity of hepatotoxicity and the presence of hepatic failure
• NAC may be used in combination with other treatments, such as activated charcoal, to manage acetaminophen overdose
• Patients with hepatotoxicity due to acetaminophen overdose should be closely monitored for signs of hepatic failure and other complications.

From the FDA Drug Label

Acetylcysteine solution, USP administered orally, is indicated as an antidote to prevent or lessen hepatic injury which may occur following the ingestion of a potentially hepatotoxic quantity of acetaminophen. Acetylcysteine has been shown to reduce the extent of liver injury following acetaminophen overdose Acetylcysteine probably protects the liver by maintaining or restoring the glutathione levels, or by acting as an alternate substrate for conjugation with, and thus detoxification of, the reactive metabolite.

N-acetylcysteine (PO) is a proven supplement for preventing or lessening hepatic injury caused by acetaminophen overdose 2 2.

• It is essential to initiate treatment as soon as possible after the overdose and, in any case, within 24 hours of ingestion.
• Its effectiveness depends on early oral administration, with benefit seen principally in patients treated within 16 hours of the overdose.

From the Research

Proven Supplements for Hepatotoxicity

• Silymarin has been shown to have a comparable pharmaceutical activity to N-acetyl cysteine (NAC) in preventing acetaminophen-induced hepatotoxicity 3, 4, 5
• Silymarin has been found to attenuate acetaminophen-induced liver damage in rats and mice 3, 4, 6
• Thymoquinone, silymarin, and N-acetylcysteine have been shown to have potential for the treatment of diseases causing liver injury, with thymoquinone appearing to be at least as effective as silymarin and NAC in some studies 7
• Silymarin and NAC have been found to protect liver tissue against oxidative stress in cats with acetaminophen intoxication 5

Key Findings

• Silymarin has been shown to prevent hepatocytes necrosis similar to NAC 3
• Silymarin has been found to improve the counteracting effects on mortality rate as compared to NAC 4
• Silymarin has been shown to ameliorate the toxic effects of acetaminophen-induced hepatotoxicity and nephrotoxicity in mice 6
• Thymoquinone, silymarin, and NAC have been found to improve the levels of alanine aminotransferase, tumor necrosis factor-α, platelet-derived growth factor-BB, and interleukin-6, which are increased by carbon tetrachloride-induced hepatotoxicity 7

Supplements and Their Effects

• Silymarin: has been shown to have a comparable pharmaceutical activity to NAC in preventing acetaminophen-induced hepatotoxicity, and has been found to attenuate acetaminophen-induced liver damage in rats and mice 3, 4, 6, 5
• N-acetylcysteine (NAC): has been shown to be effective in preventing acetaminophen-induced hepatotoxicity, and has been found to protect liver tissue against oxidative stress in cats with acetaminophen intoxication 3, 4, 7, 5
• Thymoquinone: has been found to have potential for the treatment of diseases causing liver injury, and has been shown to improve the levels of alanine aminotransferase, tumor necrosis factor-α, platelet-derived growth factor-BB, and interleukin-6, which are increased by carbon tetrachloride-induced hepatotoxicity 7