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Aged Garlic Extract Protects Against Acetaminophen Toxicity
by Carmia Borek, Ph.D.

Aged garlic extract, or KYOLIC® manufactured by Wakunaga, is an odorless supplement with high antioxidant activity. Aged garlic extract (AGE) has been reported in over 600 research publications to provide a wide range of health benefits, which include cardiovascular protection, anti-cancer, and anti-aging effects. In addition, AGE has been shown in both pre-clinical and clinical studies to protect against the toxic effects of free radical-producing environmental agents and drugs, such as acetaminophen.

Acetaminophen, also known as Tylenol or paracetamol, is the most commonly used painkiller and fever-reducing agent. Taken at high doses, this painkiller could be fatal. A detailed examination of the ingredients in the many medications found on pharmacy shelves shows that more than 100 over-the-counter cold and analgesic medicines and prescription combinations contain acetaminophen. Pain can be debilitating and as people respond to discomfort in different ways, there is often a tendency to overdose to eliminate the pain. The trouble is, that while acetaminophen reduces pain, an overdose will destroy the liver, where it is metabolized, leading to liver failure and death.

As reported to the American Association of Poison Control Centers, acetaminophen is one of the most common medications involved in overdose and acetaminophen toxicity is the cause of most acute hepatic failure, requiring transplantation. The need to prevent acetaminophen toxicity and have an antidote on hand is highly important. AGE appears to provide such protection, as seen below.

Acetaminophen Dose

The maximum daily dose of acetaminophen is 4 g in adults and 90 mg/kg in children. The toxic dose after a single ingestion is approximately 7 g in adults, but lowers in those who abuse alcohol, have a viral infection, and are malnourished or dehydrated. When taken at recommended doses, the risk of liver toxicity is extremely small.

Acetaminophen is rapidly absorbed from the stomach and small intestine. A fraction is metabolized by enzymes of the p450 family, to produce a toxic, free radical-producing substance, N-acetyl-p-benzoquinone imine (NAPQI).

In normal circumstances, when taken at recommended therapeutic doses, NAPQI is rapidly detoxified in the liver by the antioxidant, glutathione, and excreted in the urine. In acute overdose, by taking a large dose at one time, or when the maximum daily dose is exceeded over a long period of time, large amounts of NAPQI are produced, the detoxifying glutathione is used up, and the liver is overwhelmed and cannot defend itself.

The excess NAPQI causes oxidative damage in proteins, DNA, and cell membranes, leading to liver cell death and fatal liver failure. The risk of liver injury is increased by alcohol or other drug intake and reduced by an antidote.

AGE (KYOLIC) Prevents Acetaminophen Toxicity

The warning by the FDA that thousands of Americans unwittingly ingest potentially fatal doses of acetaminophen highlights the need for protection. Such protection is provided by AGE. The highly standardized odorless AGE is produced by long extraction and aging of organic fresh garlic at room temperature. The process increases antioxidant levels, well above those of the fresh bulb and converts harsh unstable compounds, such as allicin to stable health-promoting substances. AGE contains mostly stable, water-soluble organosulfur compounds, which are powerful antioxidants and are largely responsible for AGE's health benefits. They include S-allyl mercaptocysteine, a compound unique to AGE and S-allyl cysteine (SAC)—the standardized compound which is highly bioavailable at a 98% absorption rate. AGE increases cell production of glutathione that is needed for drug detoxification, including acetaminophen.

A number of studies show that AGE, SAC, and S-allyl mercaptocysteine protect the liver against acetaminophen by both preventing toxicity and as an antidote.

In a 2006 study, AGE components, SAC and S-propyl cysteine were added into the drinking water of mice for four weeks, followed by an acetaminophen treatment. Acetaminophen depleted the content of liver glutathione, increased oxidative stress, and elevated blood levels of markers of liver toxicity, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). However, the intake of SAC prevented glutathione depletion, prevented the elevation of ALT and AST, and increased the enzyme, glutathione peroxidase, which eliminates free radical-producing peroxide.

Other studies found that treatment with SAC and S-allyl mercaptocysteine protected mice against acetaminophen-induced hepatotoxicity in both the following situations: when given before acetaminophen, acting as a preventive agent; and when given after acetaminophen, acting as an antidote.

In a study on the antidote effect, S-allyl mercaptocysteine, given half an hour after acetaminophen, suppressed the increase in the toxicity marker, ALT, and prevented liver cell death; it also reduced acetaminophen-induced mortality from 43% to 0%. The study showed that S-allyl mercaptocysteine is useful as an antidote for acetaminophen overdose, acting in part by suppressing a liver cytochrome P450 activity, thereby preventing the formation of molecules that damage proteins in ways that lead to liver cell death.

A human study further confirmed the efficacy of AGE in helping prevent acetaminophen toxicity. In this clinical study, 16 subjects ingested AGE at a dose of 10 ml/day (3000 mg/day, the approximate equivalent to six to seven cloves of garlic) for 3 months. Each subject received a 1 g oral dose of acetaminophen, before the course of garlic, at the end of each month, and 1 month after the end of AGE intake. It was found that AGE increased acetaminophen metabolism and detoxification, indicating its benefit in humans in protecting the liver, and potentially preventing fatal consequences of acetaminophen-induced liver failure, when taken at high doses.

While it is best to avoid overdosing with acetaminophen, it is wise to consider preventive and therapeutic measures. AGE expedites acetaminophen detoxification and scavenges free radicals that are produced in the course of acetaminophen ingestion. The dual action of AGE as protector and antidote can help save the liver from destruction and save lives.