DR. RONA'S HEALTHWISE DIGEST

JAMA Goofs Again

DO ANTIOXIDANTS INCREASE MORTALITY?

Here we go again. It’s almost an annual occurrence. Mainstream media announces the latest bad news about the natural health care industry and the public panics. Usually it involves vitamin toxicity or “proof” that vitamins don’t work as advertised. The natural health product (NHP) industry panics.

The stories always seem to be front-page news and alarmist enough to adversely affect the health of patients reading them. Temporarily, NHP sales plummet only to rebound once it is realized by one and all that the conclusions are exaggerated at best. Without exception, the attacks are based on very poorly done studies, anecdotes or the ramblings of crackpot opponents of natural health care.

The most recent case in point is the JAMA article (2007 Feb 28;297(8):842-57) that concludes that “Treatment with beta carotene, vitamin A, and vitamin E may increase mortality.” Do we now all stop taking our daily vitamin supplements? Before we do that, let’s first examine this study.

“This is a flawed analysis…the totality of the evidence indicates that antioxidants from foods or supplements have many health benefits, including reduced risk for cardiovascular disease, some types of cancer, eye disease, and neurodegenerative disease…they are a key to an enhanced immune system and resistance to infection.”

Dr. Jeffrey Blumberg, Director of the Antioxidants Research Laboratory at Tufts University in Boston, Massachusetts
First of all, the conclusions of this JAMA study were based entirely on a statistical review of selected old data. There was really no experimental design or actual study done here. Further, it was published by the same “scientists” that denounced antioxidants in a Lancet article in 2004. The latter was dismissed as science fiction by most credible scientists but the authors are back again with even more nonsense. They discount most of the well-established scientific support for antioxidants and go on to conclude that antioxidant vitamins increase death from all causes.
Wrong Dosages Evaluated
If one wants to see whether or not a nutrient is effective in preventing or curing illness one must at least use the correct dosage. The JAMA statistical review used suboptimal, very wide and inconsistent dosage ranges for the antioxidants evaluated.
Supplement Dose range
Vitamin A (synthetic) 1,333-200,000*** IU
Alpha Tocopherol (synthetic) 10-5,000 IU
Vitamin C (synthetic) 60 – 2,000 mg
Selenium (natural) 20 – 200 mcg

Who in their right mind takes 200,000 IU of vitamin A for 3 months of time on their own? The way this review is put together one would assume that everyone does this and ends up poisoning himself or herself.
Proven Beneficial Nutrients Omitted
The nutrients that were evaluated in this negative JAMA article are a small percentage of the total available antioxidants that most people who are serious about disease prevention take on a regular basis. Isolating the four nutrients from the dozens recommended by most antioxidant authorities and drawing conclusions from those four alone is not valid.
The authors failed to include a long list of proven disease preventing nutrients such as gamma tocopherol, natural alpha tocopherol succinate and tocotrienols in the case of vitamin E, bioflavonoids like those found in bilberry and grape seed extract, CoQ10 and resveretrol just to name a few. The use of synthetic alpha tocopherol has long ago been warned about by experts in the natural health care industry and does not warrant any further study. Extrapolating its adverse effects to all natural antioxidants is unscientific.
Other very important life extending nutrients ignored by the review were omega-3 fatty acids, alpha lipoic acid, carnitine, arginine, standardized fruit & vegetable extracts, carotenoids, B-vitamins, and minerals such as calcium, magnesium and zinc.
Poor Selection of the Study Population for Too Short Duration
The studies selected for review used an average age of 62 for their subjects for an average of 3.3 years. No one in their right mind could possibly hope that the use of suboptimal doses of selected antioxidants could somehow be beneficial in prolonging life in those that had already endured a lifetime of oxidative damage.
In other words, giving 60 year old plus smokers who had been taking at least 3 or more drugs some antioxidants is like using gasoline to put out a fire. Yet, this is similar to what these authors did. Why the prestigious JAMA would allow this review to be published in the first place is the real question.
Manipulating Statistics Leads to Erroneous Conclusions
An old professor of mine at McGill University once told me that one could manipulate statistics in such a way as to “prove” that cigarette smoking is good for you. Just leave out the results of a few studies here and include the results of some poorly done studies there for your statistical review and you have that conclusion.
“One of the major premises of doing such a meta-analysis is that the studies should be comparable…here, they looked at primary prevention, treatment, old people, young people, smokers, nonsmokers. Only when they used their own criteria of what was good and what was bad were they able to show an increase in all-cause mortality."
Dr. Jeffrey Blumberg, Director of the Antioxidants Research Laboratory at Tufts University in Boston, Massachusetts
http://www.washingtonpost.com/wp-dyn/content/article/2007/02/27/AR2007022700925.html
Exclusion of over 90% of Favorable Antioxidant Studies
With the JAMA review the authors chose only 68 out of a potential of 815 studies that favorably supported the use of antioxidants in disease prevention. Out of these excluded studies, 405 failed to show any deaths at all either in the study or placebo group.
The deaths reported by the JAMA review were incorrectly reported from a 2001 study where only one death occurred in the placebo group, one death in the drug and antioxidant group and no deaths in the group given only the antioxidants (Brown BG, Zhao XQ, Chait A, et al. Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med. 2001;345: 1583-1592).

Overwhelming Antioxidant Safety and Efficacy Studies Ignored
Several hundred studies published in peer reviewed medical journals like JAMA have used large populations of individuals studied for decades (not 3.3 years) and concluded highly significant life extending benefits of antioxidant supplements. Three of the most striking of these taken from the Life Extension Foundation site rebuttal of the JAMA review (http://www.lef.org/featuredarticles/consumer_alert_020307.htm) are summarized below:
“1)A study involving over 29,092 male smokers aged 50-69 years followed prospectively for 19 years showed that men with the highest serum alpha-tocopherol levels had a 28% lower risk of total and cause-specific mortality than did those with the lowest levels, and a 21%, 29%, and 30% lower risk of deaths due to cancer, cardiovascular disease, and other causes. (Wright ME, Lawson KA, Weinstein SJ, Pietinen P, Taylor PR, Virtamo J, Albanes D. Higher baseline serum concentrations of vitamin E are associated with lower total and cause-specific mortality in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Am J Clin Nutr. 2006 Nov;84(5):1200-7).

2)A study in 3,254 people (1,260 males and 1,994 females) aged from 39 to 85 years followed from 1989 to 1995 showed that higher serum levels of carotenoids with pro-vitamin A activity significantly reduces the risk of mortality from cardiovascular disease and colorectal cancer. (Ito Y, Suzuki K, Ishii J, Hishida H, et al. A population-based follow-up study on mortality from cancer or cardiovascular disease and serum carotenoids, retinol and tocopherols in Japanese inhabitants. Asian Pac J Cancer Prev. 2006 Oct-Dec;7(4):533-46).

3)A study in aging women that showed those with the lowest levels of alpha- and beta-carotene, lutein/zeaxanthin, and total carotenoids were significantly more likely to have increasing IL-6 levels over a period of 2 years, and those aging women with the lowest selenium levels had a significantly higher 54% risk of death over a 5-year period. (Walston J, Xue Q, Semba RD, Ferrucci L, Cappola AR, Ricks M, Guralnik J, Fried LP. Serum antioxidants, inflammation, and total mortality in older women. Am J Epidemiol. 2006 Jan 1;163(1):18-26).”

For details of dozens of other such studies, see http://www.lef.org/featured-articles/consumer_alert_020307.htm

The Bottom Line

Hopelessly flawed studies like this recent JAMA review article only serves to reinforce the fact that antioxidants play a major role in disease prevention. I expect the attacks on antioxidants to continue for years to come. Maybe the next attack can be more founded in science and less in ignorance. Until then, I’ll continue taking my antioxidants and I suspect you should do so as well.

THE PUBLISHED JAMA ARTICLE ABSTRACT
Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C. Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis. JAMA. 2007 Feb 28;297(8):842-57

The Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Center for Clinical Intervention Research, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. goranb@junis.ni.ac.yu

CONTEXT: Antioxidant supplements are used for prevention of several diseases. OBJECTIVE: To assess the effect of antioxidant supplements on mortality in randomized primary and secondary prevention trials. DATA SOURCES AND TRIAL SELECTION: We searched electronic databases and bibliographies published by October 2005. All randomized trials involving adults comparing beta carotene, vitamin A, vitamin C (ascorbic acid), vitamin E, and selenium either singly or combined vs placebo or vs no intervention were included in our analysis. Randomization, blinding, and follow-up were considered markers of bias in the included trials. The effect of antioxidant supplements on all-cause mortality was analyzed with random-effects meta-analyses and reported as relative risk (RR) with 95% confidence intervals (CIs). Meta-regression was used to assess the effect of covariates across the trials. DATA EXTRACTION: We included 68 randomized trials with 232 606 participants (385 publications). DATA SYNTHESIS: When all low- and high-bias risk trials of antioxidant supplements were pooled together there was no significant effect on mortality (RR, 1.02; 95% CI, 0.98-1.06). Multivariate meta-regression analyses showed that low-bias risk trials (RR, 1.16; 95% CI, 1.05-1.29) and selenium (RR, 0.998; 95% CI, 0.997-0.9995) were significantly associated with mortality. In 47 low-bias trials with 180 938 participants, the antioxidant supplements significantly increased mortality (RR, 1.05; 95% CI, 1.02-1.08). In low-bias risk trials, after exclusion of selenium trials, beta carotene (RR, 1.07; 95% CI, 1.02-1.11), vitamin A (RR, 1.16; 95% CI, 1.10-1.24), and vitamin E (RR, 1.04; 95% CI, 1.01-1.07), singly or combined, significantly increased mortality. Vitamin C and selenium had no significant effect on mortality. CONCLUSIONS: Treatment with beta carotene, vitamin A, and vitamin E may increase mortality. The potential roles of vitamin C and selenium on mortality need further study.

REFERENCE

http://www.lef.org/featured-articles/consumer_alert_020307.htm

TYLENOL BLUES

The Perils of Painkillers
Tylenol Toxicity – and its Alternatives

By Zoltan P. Rona, MD, M.Sc.

Originally published in Vitality Magazine, March 2007
See http://www.vitalitymagazine.com/the_perils_of_painkillers

So, you think Tylenol is safe. Most of us have always assumed that Tylenol (acetaminophen) is the safest painkiller on the market. After all, it is the number one drug used in the world. While it is usually effective for mild to moderate pain, its safety is somewhat of a myth.

Acetaminophen, the generic name for Tylenol, can be found in over 200 different OTC and prescription medications. It is commonly mixed into migraine, arthritis, cough, sinus and cold remedies.
According to the U.S. FDA, acetaminophen is considered the most common cause of liver failure, accounting for at least half of the cases in the U.S. yearly.

Liver toxicity with acetaminophen is more likely when combined with heavy alcohol use, the simultaneous use of other drugs containing acetaminophen, as well as simultaneous use of drugs that affect the liver (e.g. antibiotics, anti-depressants, anti-fungals, seizure medications, the birth control pill, etc.).

Severe liver damage can occur in adults who use acetaminophen for more than 10 consecutive days at doses of 4000 mg or more per day. That’s the equivalent of eight extra strength Tylenol tablets per day. The liver toxicity dosage is lower in children (90 mg/kg) and in people who already have weakened liver function due to hepatitis, AIDS, anorexia nervosa, cirrhosis, alcoholism or other diseases. The toxic dose of acetaminophen after a single acute ingestion is 150 mg/kg in children or approximately 7000 mg in adults.

Acetaminophen is the commonest drug involved in overdoses of any kind according to the American Association of Poison Control Centers. In the U.S., it is estimated that acetaminophen results in 56,000 injuries, 25,000 hospitalizations, and 450 deaths every year. Acetaminophen is also the most common cause of liver failure requiring liver transplantation in Great Britain and the second most common cause of liver failure requiring transplantation in the United States.

Some of the symptoms of a toxic reaction to acetaminophen include nausea, abdominal pain, sweating, seizures, confusion, an irregular heartbeat, swelling, hives, difficulty breathing, unusual bleeding or bruising and closing of the throat. Diabetics should note that acetaminophen can change blood sugar levels, requiring adjustments in insulin or other diabetes medications.

Tylenol troubles are on the rise. Acute liver failure caused by acetaminophen has risen sharply from 28 percent in 1998 to 51 percent in 2003. That’s a near doubling of life threatening toxic reactions within five years. Unintentional overdoses (48%) on acetaminophen outnumber intentional (suicide attempt) overdoses (44%).

Most recently, researchers have reported that the use of acetaminophen has been linked to higher rates of asthma and chronic obstructive pulmonary disease (COPD), as well as reduced lung function. (American Journal of Respiratory and Critical Care Medicine May 1, 2005;171:966-971 and Medical News Today May 3, 2005)

What next? Marketplace Irony

The anti-stress herb kava kava was taken off the market in 2002 by Health Canada because of four reports of liver toxicity. No deaths were reported. Tylenol causes thousands of cases of liver toxicity and death in Canada each year, yet remains on the market.

Tobacco and alcohol also kill thousands in Canada each year and they also remain on the market._

Protecting Your Liver From Tylenol

If you are one of those unfortunate souls who has seemingly no choice but to take Tylenol for life, you can do a lot to prevent liver toxicity.

Acetaminophen does its damage to the liver by depleting the body of glutathione. You can offset this drug-induced deficiency by supplementing with NAC (N-Acetyl-Cysteine), an amino acid that boosts levels of glutathione. In fact, NAC is exactly what hospital emergency rooms use for acute acetaminophen toxicity. NAC is virtually harmless and can be safely taken by most adults at a dose of 1000 mg three times daily. Children under the age of 12 can take roughly half the dose._Other liver protective natural remedies include alpha lipoic acid, milk thistle, SAM (S-adenosyl-methionine) and the bioflavonoids rutin, catechin, hesperidin and quercetin._

Non-toxic Alternatives to Tylenol

When possible, everything should be done to determine the cause of pain and inflammation instead of suppressing it with a drug. Last time I checked, Tylenol was not the cure for any disease.
Stress, hormonal imbalances, nutritional deficiencies (e.g. vitamin B12, zinc, copper) or toxicities (e.g. mercury, lead, cadmium), food and chemical allergies, as well as body structure imbalances are usually at the bottom of chronic pain conditions. Sometimes a dentist or chiropractor can discover the source of chronic pain. A natural health care provider can usually help sort out the cause or causes for most people.

Until you get the opportunity to be assessed by a natural health care professional, one or a combination of the following commonly available health food store remedies may be good alternatives to Tylenol for pain control.

Ginger Root: A very effective traditional anti-inflammatory herb which also has anti-nausea effects.

Boswellia: Together with bromelain and ginger root, this herb has potent anti-inflammatory and pain relieving benefits in just about any kind of arthritis.

Bromelain: This pineapple enzyme has long been successfully used as a natural pain and anti-inflammatory remedy; it works best when taken on an empty stomach.

Curcumin: An extract of the herbs tumeric and cumin, this powerful anti-inflammatory can also protect the liver from damage caused by a long list of viruses, drugs and chemicals. The usual effective dose is 1000 mg three or more times daily.

Omega-3 Oils (EPA and DHA): Usually found in fish oil but also in hemp, Omega 3s can be anti-inflammatory in doses of 12 grams daily, reducing pain and inflammation in conditions as diverse as migraine headaches and sciatica.

Other Oils: Evening primrose oil, borage oil and black currant seed oil are all high in the essential fatty acid gamma linolenic acid (GLA) which has been found helpful in any kind of arthritis and eczema.

Capsaicin cream: An extract of cayenne pepper that can be applied to painful areas topically. It works to relieve pain by depleting the body’s supply of substance P, a chemical that transmits pain signals.

D,L-Phenylalanine: An amino acid that boosts the body’s production of its endorphins (opiate-like compounds), thereby producing pain control; the usual effective dose is 1000 mg three or more times daily between meals.

Dr. Zoltan P. Rona practices Complementary Medicine in Toronto and is the medical editor of “The Encyclopedia of Natural Healing.” He has also published several Canadian best selling books including “Return to The Joy of Health”. For more of his articles, see http://www.mydoctor.ca/drzoltanrona

References

• www.drugs.com_
• www.onlinelawyersource.com/acetaminophen/side-effects.html_
• www.emedicine.com/emerg/topic819.htm_
• www.mercola.com/2005/dec/17/the_toxicity_of_tylenol.htm_
• www.mercola.com/1998/archive/acetaminophen_deaths.htm_
• www.hc-sc.gc.ca/ahc-asc/media/advisories-avis/2002/ 2002_56bk_ e.html_
• Johnson, G.K. 1977. "Chronic Liver Disease and Acetaminophen." Annals of Internal Medicine 87: 302-4. _
• Barker, J.D., et al. 1977. "Chronic excessive acetaminophen use and liver damage." Annals of Internal Medicine 87: 299-301. _
•Prescott, L.F. 1986. "Effects of non-narcotic analgesic on the liver." Drugs 32: 129-47._

INTERNET HEALTH INFORMATION SCAMS AND RELIABLE SITES

Internet Health Information Scams

By Dr. Zoltan P. Rona

Dr. Rona is the author of several Canadian best selling books and
practices complementary/integrative medicine in Toronto. To read
more of his articles, see http://www.mydoctor.ca/drzoltanrona

A few years ago one of my patients brought me an article from the
Internet that claimed I advise my patients to drink their own urine and
that I got my Masters Degree from the Moonies. Of course, this is
nonsense (I warn people not to drink their urine and I got my Masters
from the University of Bridgeport who provided the training at the Toronto
General Hospital). This sort of experience illustrates some important
points to consider about health information you find on the Internet.
More often than not, web sites are recruiting vehicles for some multi-level
marketing company, the sale of drugs and food supplements or
promoting a quasi-religious or political philosophy. The health information
they provide may be heavily biased. Due to practitioner turf wars and
philosophical differences between various health disciplines (e.g.
mainstream medicine vs. homeopathy), there is bound to be huge
differences of opinion on the same health issue.

For example, there are “quackwatch” web sites that dismiss or denigrate
just about every type of health advice that does not include drugs or
surgery. I wouldn’t mind these people all that much if they attempted to
be balanced in their reporting. Most of these obsessively hypercritical
web sites claim that all chiropractors, naturopaths, homeopaths,
acupuncturists, health book and magazine authors are quacks. Yes,
even you may be on their quack list. Check these sites out:
Dr. Terry Polevoy, an acne specialist and self-proclaimed Canadian 1)
quackwatcher, uses his web site to take pot shots at just about
every type of medical alternative. Hundreds of complementary or
integrative medical people, including myself, have been
“polevoyed.” No rest for this lively whiner. See
http://www.healthwatcher.net/Quackerywatch/index.html but also
see http://www.quackpotwatch.org/opinionpieces/gunships.htm
Dr. Stephen Barrett, the American equivalent of pimple popping 2)
Polevoy, has a far more extensive quackwatcher site
(http://www.quackwatch.org/) but, also see
http://www.healthfreedomlaw.com Needless to say, both Barrett
and Polevoy are involved in numerous lawsuits.

For some reason, these folks seem to begrudgingly approve of Dr.
Andrew Weil, the American health guru who basically shares the same
health philosophy as many of the health professionals the quackbusters
vilify. Polevoy claims Weil has gone “mainstream”. Could this have
anything to do with Weil’s appearance on the front page of TIME
magazine or his numerous appearances on CNN, both media heavily
sponsored by drug companies?

The quackwatchers cleverly omit the fact that thousands of people are
killed off each year by drugs like Vioxx prescribed by mainstream
medical doctors (see http://www.adrugrecall.com/). They also have no
comment on the fact that conventional medical doctors and their FDA
approved prescription drugs are the third leading cause of death in North
America (see JAMA July 26, 2000; 284(4): 483-5). Sure, we have a few bad
apples in the alternative medical world, but let’s not dismiss all of them
because of their health philosophy.

Evaluating the reliability and credibility of Internet health information is
challenging at best. There are, however, a few general guidelines that
usually help you separate health fact from commercial/political fiction.
Always remember that anybody can publish and promote whatever they
want on the Internet. There is no health information censorship (at least
not yet). The authority and reputation of the source is the most important
factor.

The following are some general guidelines for what to think about when
searching for health information on the Internet. They also apply to popular
health books and magazines. If any of you reading this have any other
suggestions to add to these, please feel free to contact me by email
(zoltan77@bellnet.ca).

Usually Reliable/Credible Health Information Characteristics

Author easily identified by relevant professional qualifications, a trusted
health organization, University or professional body
The health information is referenced by scientific publications, clinical
evidence or is peer reviewed
The information is current, relevant and consistently updated by a
contactable Webmaster
Educational and non-profit web sites are usually more reliable than
commercial ones

Usually Unreliable/Dubious Health Information Characteristics

Author not easily identified by qualifications but connected to a web site
used to sell a product or promote a particular political, commercial or
personal point of view (e.g. various quackwatcher sites)
The health information is rambling, narrative, unreferenced and
anecdotal for the most part (e.g. most multi-level marketing supplement
sites)
The information is dated, irrelevant and the Webmaster cannot be
contacted to verify or update facts
Commercial web sites with shopping carts, demands for credit card
information and personal information

My Web Site Recommendations

The following web sites meet the criteria for usually reliable and credible
information and have minimal commercial content. These are all good
places to start your health information quest:

1) McMaster’s Alternative Medicine site
(http://hsl.mcmaster.ca/tomflem/altmed.html) attempts to be the richest
and most comprehensive resource for complementary/integrative
medical information. McMaster University was one of the first in North
America to offer complementary medicine training for its medical
students and is usually on the cutting edge of health information.
2) The National Center for Complementary and Alternative Medicine
(http://nccam.nih.gov/) is a U.S. government sponsored site with a rather
conservative approach to health care topics and issues. For the more
scientifically inclined, this may be the best choice but the information is
not as user friendly.
3) HealthWorld Online (http://www.healthy.net) is a multi-authored site
with dozens of articles by well-respected author, Dr. Elson Haas.
Although many of the articles were originally published in the 1990s, the
information is still accurate and regularly updated. Articles are not tied
into product sales in most cases.
4) Dr. Joseph Mercola’s site (http://www.mercola.com/) is chock full of
interesting and very current health information. Mercola regularly reviews
published medical journal articles and keeps a wide eye open for health
care system abuses. His free weekly newsletter is a great way to keep
up with all the latest. The sales pitches and political rhetoric on the site
are only mildly annoying.