Most people have the notion that over-the-counter (OTC) medications-in particular, non-narcotic analgesic drugs (pain-killers)-must be completely safe, or else they would require a prescription. Some OTC pain medications, such as aspirin and non-steroidal anti-inflammatory drugs (NSAIDs), do have beneficial effects; aspirin has long been recommended for use by heart patients, and ibuprofen has been found to slow the progression of Alzheimer's disease and some cancers (Mitchell et al. 2000, 2001). These drugs are recommended by the Foundation for use in treating those diseases.

However, acetaminophen (sold under Tylenol and other brand names) has dangerous side effects that most people are not aware of. Many people either use this class of drug chronically or take higher-than-recommended doses, not realizing that they are causing liver, and kidney damage. The long-term use of acetaminophen medications can cause other problems as well.

Acetaminophen

Acetaminophen is one of the more potentially dangerous analgesic drugs. An intentional overdose can be fatal, and chronic use may cause liver and kidney damage (McLaughlin et al. 1985; Siegers et al. 1989; Price et al. 1991; Bonkovsky et al. 1994; Blakely et al. 1995).

When a person takes acetaminophen, it is metabolized by a number of metabolic systems in the liver, including one called the P450 system. This results in an intermediate by-product, or metabolite, that is very reactive and can kill liver cells. This intermediate metabolite is normally converted to a harmless final metabolite by an antioxidant in the liver called glutathione (Uhlig et al. 1990; Deleve et al. 1991; Richie et al. 1992). A large dose of acetaminophen reduces the glutathione supply, resulting in progressive necrosis of the liver, sometimes evidenced in as little as 5 days. Alcoholics and those on certain medications that stimulate the P450 system are at particular risk because, with increased P450 activity, more toxic intermediate is created than there is glutathione available to further metabolize it to something harmless. Although not fatal, chronic acetaminophen use decreases the functional capacity of the liver.

Acetaminophen can also cause permanent kidney damage when taken over extended periods of time. This damage can be lethal to those with underlying kidney disease. The Food and Drug Administration does not require the manufacturers of Tylenol and other brands of acetaminophen to adequately warn people with kidney disease to avoid this pain medication. However, for those in chronic pain who cannot find relief from natural pain relief therapies (see Pain and Arthritis protocols), it is suggested that Tylenol and other brands of acetaminophen be used sparingly.

To illustrate how dangerous acetaminophen can be, one study showed that people who used acetaminophen with other pain relievers on a regular basis had a three- to eightfold increase in their risk of kidney cancer. Kidney cancer is very difficult to treat. The liver-kidney-heart muscle toxicities and the cancer risks of analgesic drugs have not been reported by most media sources, which reap tremendous profits from the advertising of pain relief products.

Acetaminophen poisoning is a toxic reaction resulting from the ingestion of excessive doses of the drug. In adults, dosages exceeding 10 to 15 grams can produce liver failure and dosages exceeding 25 grams can be fatal. Symptoms such as nausea and vomiting, profuse sweating, pallor, and oliguria (scanty amounts of urine) are associated with the onset of acetaminophen poisoning. Jaundice and pain in the upper abdomen, hypoglycemia, encephalopathy, abnormal functioning of brain tissue, and kidney failure may become apparent as drug toxicity increases.

Headache and Analgesic Rebound

One of the more common reasons for chronic analgesic use is for the treatment of headaches. Many patients suffer from chronic headaches for years, some conditions lasting over 10 years in duration. These patients have seen numerous physicians, including neurologists and pain specialists, and have received countless studies, including MRIs and CTs of the brain. They have also had several diagnoses over the course of their treatment. A large proportion of these patients suffered from a condition that has been described in the literature as analgesic rebound.

Simply stated, the problem began when the patients first experienced a few headaches in succession and began taking analgesic medications. They quickly increased the dose and found that they could not survive without the medications. However, the medications failed to totally relieve their headaches. The treatment, from the doctor's perspective, is simple: stop taking all pain medications. The cause of the headaches is a rebound effect from the cessation of large dosages of analgesic medications. If the patients can get through several weeks of total cessation of the use of all analgesic medications, the headaches will cease. Needless to say, it is not surprising how difficult it is to convince them of this!

Headache sufferers may attempt various types of treatment to help break the cycle, including acupuncture, orthomolecular dosages of intravenous vitamin C, intravenous dimethylsulfoxide (DMSO), and short-time low-dose corticosteroid administration. Ultimately, it may be the cessation of all analgesic drug use that finally ends the headache. However, to help deal with the pain during the two-week treatment program, the administration of intravenous DMSO or short-term corticosteroid has been most helpful. Next to "cold turkey," intravenous DMSO is probably the best way to go. (See the Migraine protocol.)

Treatment

Some people alternate other types of OTC pain-relieving drugs, such as aspirin, Advil, and Naprosyn, to avoid using acetaminophen on a daily basis. Alternating their usage may help to reduce their toxicity.

If a person attempts to commit suicide by taking an entire bottle of acetaminophen, the emergency room doctor will administer an antioxidant drug called Mucosil (Mucomyst). If administered in time, Mucosil can save the patient's life by inhibiting free-radical damage to the liver caused by acetaminophen-induced depletion of hepatic glutathione (Deleve et al. 1991). The active ingredient in Mucosil is the nutrient N-acetylcysteine (NAC). NAC suppresses the toxic free radicals generated by ingested acetaminophen. If you have to take acetaminophen, we suggest you take 600 mg of the amino acid N-acetylcysteine or L-cysteine and at least 1 gram of vitamin C with each dose of acetaminophen.

NOTE: When using the drug Mucosil (N-acetylcysteine) to treat acute liver failure from acetaminophen overdose, it is crucial that the drug be administered immediately and that it be continued for at least 36 hours in all cases (Clemmesen et al. 1996). Optimal results occur when NAC is administered within 10 hours of acetaminophen overdose. NAC is also effective when given after 15 hours of acetaminophen poisoning (Graudins et al. 1995; Jones 1998). Treatment with N-acetylcysteine (NAC) should not be discontinued until all clinical signs of toxicity have subsided. Permanent liver injury can occur if NAC therapy is discontinued too soon. Patients who develop chronic liver failure should be treated with a prolonged course of NAC under a physician's care (Kind et al. 1996).

Another approach to protecting against acetaminophen-induced free-radical liver damage is to take one capsule of a multinutrient formula that contains glutathione, vitamin C, and cysteine with each dose of acetaminophen. This antioxidant formula will provide significant protection to the liver. Additionally, for those who must take acetaminophen chronically, the herb milk thistle (silibinin) may offer some liver protection by increasing the amount of the protective antioxidant glutathione (Zhao et al. 1999). For those whose liver function has been compromised by analgesics or other toxins, treatment with SAMe (S-adenosylmethionine) may help to repair the liver (Lieber 1997).

There are no nutrient supplements known to protect against acetaminophen-induced kidney damage, although the amino acid taurine (1000-3000 mg a day) and high doses of vitamin E succinate (800-1200 IU a day) might be helpful.

Polyenylphosphatidylcholine

Polyenylphosphatidylcholine (PPC), a supernutrient, is a 94-95% pure mixture of polyunsaturated phosphatidylcholines extracted from soybeans that appears to protect against liver injury evoked by fibrosis, oxidative stress, medicinal poisoning such as acetaminophen, or alcohol abuse.

When taking high doses of analgesics such as ibuprofen, aspirin, naprosyn or prescription anti-inflammatory drugs, PPC can assist in protecting the gastric mucosa, making the stomach less vulnerable to irritation, inflammation and ulceration (Anand BS et al 1999; Dunjic BS. et al. 1993).

Research confirms that silibinin (milk thistle), when complexed with phosphatidylcholine at a dosage of 400 mg/kg, was protective against acetaminophen hepatotoxicity. The expected increase in liver enzymes, often observed during liver trauma, was not as extreme when silibinin and phosphatidylcholine was administered (Conti et al. 1992). The protective effect of silibinin is probably related to its antioxidant activities and to stimulating the hepatic synthesis of RNA and proteins.

The source of the phosphatidylcholine also determines its effectiveness. Soybean-derived phosphatidylcholine, administered 2 hours prior to acetaminophen, lessened the increase in serum transaminase activity, whereas egg yolk phosphatidylcholine failed to protect against acetaminophen hepatotoxicity (Jaeschke et al. 1987).

Phosphatidylcholine has a history of not only being liver-protective, but also being able to enhance the bioavailability of various nutrients and herbs, such as milk thistle. The following research corroborates this finding.

Chemically intoxicated mice were protected from liver damage when treated with PPC liposomes and vitamin E acetate. Liver protection was not evidenced when phosphatidylcholine was removed from the complex, suggesting that vitamin E and liposomes lost effectiveness without PPC. Vitamin E is, however, thought to improve the protective spectrum, illustrating the usefulness of phosphatidylcholine in enhancing the delivery and utilization of beneficial nutrients (Werner et al. 1990).

Acetaminophen poisoning is not unlike any other massive assault upon the liver caused by substances known to degrade liver performance. Protocols to assist the liver in recovery from diverse poisons may have universal application, such as the treatment of an alcoholic liver. A study conducted at the Mount Sinai School of Medicine and Alcohol Research and Treatment Center, determined that PPC decreased the activity of CYP2E1, part of the cytochrome P450 detoxification family. It was also shown that PPC opposes hepatic oxidative stress and fibrosis (Lieber 2000). Fibrosis is a state of proliferation of fibrous connective tissue that forms as scar tissue replaces normal tissue lost through injury or infection. The fibrous connective tissue spreads over or replaces normal organ tissue. Because of the benefits described with PPC usage, it is now being tested clinically for the prevention and treatment of liver disease in the alcoholic.

Summary

The following protocol is intended to support organs susceptible to damage by acetaminophen, either through prolonged usage or alcohol-acetaminophen interactions. This program is not intended to replace medical attention if acetaminophen poisoning is suspected.

For more information: Contact the American Academy for Advancement of Medicine at (800) 532-3688 to find a physician in your area utilizing intravenous DMSO.

Product availability: GastroPro (polyenylphosphatidylcholine (PPC)), N-acetylcysteine (NAC), L-cysteine, vitamin C, L-glutathione, silibinin, SAMe, taurine, and vitamin E are available by phoning (800) 544-4440 or order online.