More Pain Relievers Called Into Question

Study Stirs Concern About Heart Safety of Over-Counter Drugs

Associated Press

April 19, 2005

By Marilynn Marchione

“With prescription drugs Vioxx and Bextra already pulled from the market, a study has

raised disturbing questions about the heart safety of over-the-counter pain relievers such as

Advil, Motrin and Aleve.” Those taking the “drugs for at least 6 months had twice the risk of dying of a heart attack, stroke or other heart-related problem.” The study was released at an American Association for Cancer Research conference in Anaheim. “The findings add to the suspicion that the heart risk extends beyond the so-called COX-2 drugs – Bextra, Vioxx and Celebrex – to the larger family of medications known as non-steroidal anti-inflammatory drugs, or NSAIDs, which include naproxen, ibuprofen and virtually all other over-the-counter pain relievers.” “’To the best of our knowledge, these are the first data to support putting a [black] box warning on NSAIDs, not just COX-2s’ said Dr. Andrew Dannenberg, a Cornell University scientist who helped do the study.” “The NSAID users were dying at twice the rate of the others from heart related

problems.” “Risk was highest among ibuprofen users who were nearly three times more likely to

die of cardiovascular disease than non NSAID users.”

USA TODAY reported the following on this study, June 1, 2005 Study Links Pain Relievers and Breast Cancer, by Rita Rubin

“The latest study, out today in the Journal of the National Cancer Institute, is the first

to suggest that long-term ibuprofen or aspirin use might actually raise the risk of breast

cancer.” “Marshall’s (Dr. Sarah Marshall from USC) study analyzed data on 114,460 women in

the ongoing California Teachers Study. The women were 22 to 85 years old and free of breast

cancer when they enrolled in the study a decade ago.” “When the scientists broke their findings down by pain reliever or type of breast cancer, they found:”

• “Women who took ibuprofen daily for at least 5 years were about 50% more

likely to be diagnosed with breast cancer than those who did not take the drug regularly.”

• “Women who took aspirin daily for at least 5 years were 80% more likely to

develop breast cancers that were not sensitive to the hormones estrogen or progesterone

than women who were not regular users of aspirin.”

The Danger Of Mixing Candy And Poison

By Tim Davern, MD, a liver transplant specialist at the

University of California, San Francisco

San Francisco Chronicle, August 14, 2004

“First Do No Harm” is a cornerstone of modern medicine. “I think the practice of combining acetaminophen (Tylenol is one popular brand) and an opiate, such as hydrocodone bitartrate, together as a single drug (as Vicodin does) defies logic, if not common sense.” Acetaminophen is a “potent dose-dependent poison for the liver; simply stated, if you take too much, your liver dies.”

Acetaminophen overdose is the “leading cause of acute liver failure in the United States today.”

On the other hand, opiates, such as hydrocodone bitartrate and codeine, while safe for the liver, are highly addictive. “Vicodin is currently the most popular prescription drug in the United States.”

Some patients become addicted to the opiate component of Vicodin and consume increasing amounts of acetaminophen, “ultimately leading to acute liver failure.” “With overwhelming liver injury from acetaminophen, what follows is a particularly grisly death punctuated by bleeding, confusion, coma and, for still largely unclear reasons, brain swelling, damage and death.” “Patients typically take too much acetaminophen for fever or pain over several days, not realizing the potential for liver damage.” “Many are unaware that acetaminophen is contained in dozens of over-the-counter cold and flu preparations.” “This situation is particularly tragic in young children accidentally overdosed with acetaminophen, typically in the setting of a flu-like illness, by well-intentioned but misinformed parents.” Acetaminophen packaging should have better warning labels, and should not be sold in 1,000 pill mega-bottles. Acetaminophen-opiate combinations [like Vicodin] should be removed from the market. “The prescription rules in California have made it far easier for physicians to prescribe an acetaminophen-opiate combination, such as Vicodin, than a pure opiate, such as codeine, although the former is far more dangerous.” The FDA banned Ephedra, which “contrasts with its puzzling, relatively meager efforts to prevent acetaminophen hepatotoxicity, which kills far more Americans each year than Ephedra.”

Take This Painkiller Carefully

Medical News That Matters

Second Opinion

By Isadore Rosenfeld, MD

Parade, February 19, 2006, pg. 6

“Acetaminophen, whose best know brand name is Tylenol, is one of the most widely used nonprescription painkillers is the US.” “Overdosing with is the leading cause of serious poisoning in this country.” “Every year, too much acetaminophen accounts for 50,000 emergency

room visits, 42% of liver failures, and an average of 458 deaths.” “Never take more than 4,000mg a day—eight 500mg extra-strength capsules.” Numerous other drugs also contain acetaminophen, including Nyquil, Sudafed, Alka-Seltzer, Sinutab, Contac, Actifed, etc. “If you have two or three alcoholic drinks or more a day, be sure to consult your doctor before taking Tylenol.” “The symptoms of acetaminophen overdose are nausea, vomiting, abdominal pain and lack of appetite.” “The specific antidote is N-acetylcysteine (NAC).” [Recall, N-acetylcysteine (NAC) works because it elevates levels of the antioxidant and detoxifier, glutathione.

Dangers of Tylenol (Acetaminophen)

Dan Murphy, DC

In 1994, researchers from JohnsHopkinsMedicalSchool published in the New England Journal of Medicine an article noting (1):

Risk of Kidney Failure Associated With the Use of Acetaminophen, Aspirin, and Nonsteroidal Anti-inflammatory Drugs

New England Journal of Medicine, December 22, 1994.

“People who take analgesic drugs frequently may be at increased risk of end-stage renal disease (ESRD).” “Heavier acetaminophen use was associated with an increased risk of end-stage renal disease in a dose-dependent fashion.” Those who took 105 – 365 acetaminophen pills per year had a 40% increased risk of end-stage renal disease compared to those who took 2 – 104 acetaminophen pills per year. For some, the risk of end-stage renal disease was as great as a 140% increased risk. For those who took more than 365 acetaminophen pills in a year, the increased risk of end-stage renal disease was 110%. For some, the increased risk of end-stage renal disease was as high as 270%. For those who took more than 1000 pills containing acetaminophen in their lifetime (compared to those who took fewer than 1000 acetaminophen–containing tablets), their increased risk of end-stage renal disease was 100%. For some, the increased risk of end-stage renal

disease was as high as 220%. For those who took more than 5,000 pills containing acetaminophen in their lifetime, their increased risk of end-stage renal disease was 140%.

For some, the increased risk of end-stage renal disease was as high as 380%. The increased risk for end-stage renal disease noted in this study was adjusted for race, sex, age, and intake of other analgesic drugs. The authors noted that 8 - 10 % of the overall incidence of end-stage renal disease is attributable to acetaminophen use. The authors concluded, “People who often take acetaminophen have an increased risk of end-stage renal disease.”

In 1997, researchers from the Department of Internal Medicine, University of Texas Southwestern Medical Center, published in the New England Journal of Medicine an article noting (2):

Acetaminophen Toxicity in an Urban CountyHospital

New England Journal of Medicine, October 16, 1997

Acetaminophen ingestion accounts for 12% of all patients hospitalized with drug overdoses. Acetaminophen ingestion accounts for 40% of patients with acute liver failure.

In 2004, Tim Davern, MD, a liver transplant specialist at the University of California, San Francisco, published (3):

The Danger Of Mixing Candy And Poison

San Francisco Chronicle

August 14, 2004

“First Do No Harm” is a cornerstone of modern medicine. “I think the practice of combining acetaminophen (Tylenol is one popular brand) and an opiate, such as hydrocodone bitartrate, together as a single drug (as Vicodin does) defies logic, if not common sense.” Acetaminophen is a “potent dose-dependent poison for the liver; simply stated, if you take too much, your liver dies.” Acetaminophen overdose is the “leading cause of acute liver failure in the United States today.” On the other hand, opiates, such as hydrocodone bitartrate and codeine, while safe for the liver, are highly addictive. “Vicodin is currently the most popular prescription drug in the United States.” Some patients become addicted to the opiate component of Vicodin and consume increasing amounts of acetaminophen, “ultimately leading to acute liver failure.”

“With overwhelming liver injury from acetaminophen, what follows is a particularly grisly death punctuated by bleeding, confusion, coma, brain swelling, damage and death.” “Patients typically take too much acetaminophen for fever or pain over several days, not realizing the potential for liver damage.” “Many are unaware that acetaminophen is contained in dozens of over-the-counter cold and flu preparations.” “This situation is particularly tragic in young children accidentallyoverdosed with acetaminophen, typically in the setting of a flu-like illness, by well-intentioned but misinformed parents.” Acetaminophen packaging should have better warning labels, and should not be sold in 1,000 pill mega-bottles. Acetaminophen-opiate combinations [like Vicodin] should be removed from the market. “The prescription rules in California have made it far easier for

physicians to prescribe an acetaminophen-opiate combination, such as Vicodin, than a pure opiate, such as codeine, although the former is far more dangerous.” The FDA banned Ephedra, which “contrasts with its puzzling, relatively meager efforts to prevent acetaminophen hepatotoxicity, which kills far more Americans each year than Ephedra.”

In 2006, regular PARADE columnist Isadore Rosenfeld, MD, publishes (4):

Take This Painkiller Carefully

Medical News That Matters

Second Opinion

By Isadore Rosenfeld, MD

Parade, February 19, 2006, pg. 6

“Acetaminophen, whose best know brand name is Tylenol, is one of the most widely used non-prescription painkillers is the US.” “Overdosing with it is the leading cause of serious poisoning in this country.” “Every year, too much acetaminophen accounts for 50,000 emergency room visits, 42% of liver failures, and an average of 458 deaths.”

“Never take more than 4,000mg a day—eight 500mg extra-strength capsules.” Numerous other drugs also contain acetaminophen, including Nyquil, Sudafed, Alka-Seltzer, Sinutab, Contac, Actifed, etc. “If you have two or three alcoholic drinks or more a day, be sure to consult your doctor before taking Tylenol.” “The symptoms of acetaminophen overdose are nausea, vomiting, abdominal pain and lack of appetite.” [NOTE: these are symptoms that somemay take Tylenol for, flu-like symptoms.] “The specific antidote is N-acetylcysteine (NAC).” N-acetylcysteine (NAC) works to save the liver following acetaminophenpoisoning because it elevates levels of the antioxidant and detoxifier, glutathione(5).

In 2005, researchers associated with HarvardMedicalSchool published in the American Heart Association journal Hypertension, an article noting (6):

Non-Narcotic Analgesic Dose and Risk of Incident Hypertension in US Women Hypertension

September 2005

Acetaminophen [Tylenol, Atasol, Anacin-3, Panadol, Excedrin {has acetaminophen, aspirin, and caffeine}], is one of the most commonly used drugs in the United States.

Compared with women who did not use acetaminophen, older women who took >500 mg per day had a 93% increased risk of hypertension. Younger women who took >500 mg per day of acetaminophen had a 99% increased risk of hypertension. Compared with non-users of acetaminophen, older women who consumed >500 mg per day for headache had a 240% increased risk of hypertension. Compared with non-users of acetaminophen, younger women who consumed >500 mg per day for headache had a 370% increased risk of hypertension.

Higher daily doses of acetaminophen significantly increase the risk of hypertension in women. Acetaminophen [Tylenol, etc.] impairs renal function by depleting glutathione, leading to renal endothelial dysfunction. Clinicians commonly do NOT understand that acetaminophen is NOT safe, and causes significant hypertension.

There are three nutritional strategies to boost levels of glutathione to protect oneself or patients against the toxicity of acetaminophen (Tylenol) and other drugs, as well as protect our bodies from other toxins such as mercury, lead, cadmium and aluminum (5):

1) Take B6, B12, Folic Acid: they help the body convert the harmful amino acid

homocysteine into the beneficial amino acid cysteine. Cysteine is the rate-limiting

factor in the construction of the antioxidant/detoxifier glutathione. (I use Complete

Omega-3 Co-Factors From Nutri-West: 800-443-3333).

2) As noted above, take N-Acetyl Cysteine, or NAC. (I use Complete Glutathione

From Nutri-West: 800-443-3333).

3) Consume undenatured whey protein. According to Dr. Gutman (5),

undenatured whey protein is probably the best method to elevate one’s levels of

glutathione. The Nutri-West product is called Complete Whey-G.

References

1) Perneger TV, Whelton PK, Klag MJ; Risk of kidney failure associated with the use of acetaminophen, aspirin, and nonsteroidal antiinflammatory drugs; New England Journal of Medicine; Dec. 22, 1994;331(25):1675-9.

2) Schiodt FV, Rochling FA, Casey DL, Lee WM; Acetaminophen toxicity in an urban county hospital; New England Journal of Medicine; Oct 16, 1997; 16;337(16):1112-7.

3) Davern T; The Danger Of Mixing Candy And Poison; San Francisco Chronicle; August 14, 2004.

4) Rosenfeld I; Take This Painkiller Carefully; Medical News That Matters, Second Opinion; Parade, February 19, 2006, pg. 6.

5) Gutman J; Glutathione, Your Body’s Most Powerful Protector, Kudo.ca Communications, 2002.

6) Forman JP, Stampfer MJ; Curhan GC; Non-Narcotic Analgesic Dose and Risk of Incident Hypertension in US Women; Hypertension; September 2005;46:500.

Government Considers Stronger Warning Labels for Tylenol

Extra Dose of Tylenol Can be Deadly

Taking More Than Recommended, Even Once, Can Cause Liver Failure

Friday, June 02, 2006

Andy Dworkin

Newhouse News Service

THIS AUTHOR NOTES. IN PART:

“Plagued by nagging colds, sore backs, throbbing heads and life's other aches and pains, millions of people reach for Tylenol.” “And if one dose doesn't stop the pain, maybe two or three will.” “If you do that, you're courting trouble: An overdose of acetaminophen, the popular painkiller in Tylenol and other brands, sends thousands of U.S. residents to the hospital each year, killing hundreds.” For years, acetaminophen overdose has been the main reason people call poison-control centers. “It's the leading cause of death in poison-control cases.” Studies show overdoses of acetaminophen [Tylenol, etc.] have become the nation's chief cause of acute liver failure. “Up to half of these poisonings appear to be accidental.” “The federal government is considering more-severe warning labels on over-the-counter acetaminophen drugs.” “Nobody should ever exceed 4,000 milligrams [of acetaminophen] per day.” The daily maximum equals eight Extra Strength Tylenols. “Doctors worry that some overdoses stem from people who combine several of the 600-plus-milligram acetaminophen drugs and don't realize how much they're ingesting.” If you regularly have three or more alcoholic drinks in a day, you may develop problems at lower doses of acetaminophen or other painkillers. Acetaminophen is the nation's most popular medicine. 2

“About a fifth of U.S. adults, or 45 million people, take acetaminophen in any week.” “Nearly 10 percent of U.S. residents under 18 take acetaminophen in any week, roughly 7 million kids.” A serious acetaminophen overdose can creep up: A person may feel fine, maybe just nauseated, for a day or two before the crisis hits. “Acetaminophen was the reason for 133,000 calls to U.S. poison-control centers in 2004. More than half of those cases needed treatment in a healthcare facility.” ER doctors can treat acetaminophen overdoses in the first 12 to 24 hours. “Overdoses increasingly cause acute liver failure, a disastrous organ collapse that hits quickly.” Years ago, hepatitis was the main cause of this life-threatening condition, which strikes about 2,000 U.S. residents each year. But acetaminophen is now the No. 1 cause of liver failure. Acetaminophen caused 42 percent of the acute liver failures in the 1998-2003 study [Acetaminophen-induced acute liver failure: Results of a United States multicenter, prospective study; Hepatology (American Association for the Study of Liver Diseases), Volume 42, Issue 6, December 2005, Pages 1364-1372], including 51 percent in the final year. “Roughly half of acetaminophen overdoses seemed accidental. Those patients said they took an average of 7,500 milligrams a day, usually for less than a week.”