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Hello all,

Am I wrong to think that antioxidants are consumed by tumors for their

growth? Have I read this incorrectly?

Thanks!!

MM

Plasma cronutrient antioxidant in cancer patients.

Abiaka CD, Al-Awadi FM, Al-Sayer H, Gulshan S, Behbehani A, Farghaly M.

Department of Medical Laboratory Science, Kuwait University, Sulaibikhat.

The distribution of breast, colon, gastric, thyroid, oral, rectal,

pancreatic and renal cancers were determined in 71 Kuwaitis, 45 other Arabs,

and 26 Indians. Plasma levels of micronutrient antioxidants, retinol,

alpha-tocopherol, lycopene, and beta-carotene were measured in the groups

and in 90 matched controls for comparison. Cholesterol was measured to

determine its association with the micronutrient antioxidants. Pancreatic

cancer occurred exclusively in Kuwaitis, while breast and colon cancers were

disproportionately higher in Kuwaitis than in the other groups.

Micronutrient antioxidant levels were similar in the groups, except for

higher lycopene levels in Kuwaitis. In most instances, the micronutrient

antioxidants, except beta-carotene, decreased significantly in levels in

patients than in controls. Low levels of retinol, lycopene, and

beta-carotene were strongly associated with pancreatic cancer. Compared to

controls, significantly increased levels of beta-carotene occurred in

breast, colon, thyroid, and renal cancers; increased lycopene occurred in

oral cancer, and increased alpha-tocopherol occurred in pancreatic cancer.

Alpha-tocopherol strongly correlated with cholesterol. Generally, changes in

alpha-tocopherol/ cholesterol ratios mimicked those of alpha-tocopherol

levels. Micronutrient antioxidant levels were significantly lower in male

patients than female patients. Age showed a negative but statistically

insignificant relationship with micronutrient antioxidants. Lycopene

strongly correlated with alpha-carotene and alpha-tocopherol with retinol.

Among the patients, all micronutrient antioxidants except retinol decreased

significantly in levels in smokers than nonsmokers, suggesting

susceptibility to cigarette smoke oxidative stress. We conclude that

micronutrient antioxidant depletions and altered associations may imply

tumor utilization or antioxidant burden in oxidative stress or both.

Furthermore, the incidence of pancreatic, colon and breast cancers among

Kuwaitis warrants further study.

PMID: 11425266 [PubMed - in process]

mi

_________________________________________________________________

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Guest guest

On Sun, 22 Jul 2001 10:03:50 +0000

" Mambo Mambo " <mambomambo@...> wrote:

> Hello all,

> Am I wrong to think that antioxidants are consumed by

> tumors for their

> growth? Have I read this incorrectly?

> Thanks!!

> MM

> Plasma cronutrient antioxidant in cancer patients.

> Abiaka CD, Al-Awadi FM, Al-Sayer H, Gulshan S, Behbehani

> A, Farghaly M.

> Department of Medical Laboratory Science, Kuwait

> University, Sulaibikhat.

---

> We

> conclude that

> micronutrient antioxidant depletions and altered

> associations may imply

> tumor utilization or antioxidant burden in oxidative

> stress or both.

We only have an observation without proof of mechanism or

causality. If we can reliably combine this observation with

the results of other studies, we could make the following

hypotheses:

1. Higher antioxidant levels generally reduce the incidence

of cancers.

2. Higher antioxidant levels don't generally reduce the

growth rate of existing cancers and may increase them either

by competing with other protective factors or by being

metabolized into pro-oxidant products. Both mechanisms were

implicated in the failed tests of beta-carotene for

protection of continuing smokers.

3. Tumors, like any growing tissue, will consume a

disproportionate share of all nutrients but especially

glucose and cholesterol. Their higher rate of metabolism

will also generate a disproportionate share of oxidative

products that the body must eliminate. Both mechanisms can

reduce plasma levels of antioxidants.

The relationship of antioxidants to cancers is still under

investigation, thankfully we have grown beyond the " magic "

belief that all antioxidants combat all cancers at all

stages. Since radiation as well as many cancer drugs

function by inflicting oxidative damage on the cancer cells,

we'd not want to provide " aid and comfort " to the enemy.

Bob Cruder

---------------------

Carlin: " I've given up on the whole human race. I think a

big, good-sized comet is exactly what this species needs.

Question Are we on the big slide down?

Carlin: " It's called CTD – circling the drain. "

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Hello all, a recent article that questions antioxidant mantra:

 

Special to The Washington Post

Tuesday, August 7, 2001; Page HE01

It used to be so simple, a battle between good and evil.

Rogue chemicals called free radicals roam about the body like brazen street

punks, the story went, smashing cellular walls and roughing up innocent DNA

molecules, causing cancers and the diseases of middle and old age.

Their flagrant disregard for the law would continue unchecked if it weren't

for swashbuckling antioxidants swooping in on the wings of dietary

supplements, disarming the free radicals of their menacing electrons and

converting them into respectable molecular citizens.

At least that's how the theory went. And the public bought it -- both the

story and millions of doses of antioxidant supplements, which they believed

would reduce disease, boost system performance and maybe even slow the aging

clock. But as a bewildering cascade of contradictory, inconclusive and

outright negative research reports over the past several years suggests, the

human body isn't governed by a B-movie script. The antioxidant story isn't

as simple as some -- largely, those who make and sell them -- would have us

believe.

" Free radicals are as good as they are bad, " says Walter Bortz of Stanford

University Medical School. He is a past president of the American Geriatric

Society and author of several popular books on aging and scientific articles

on vitamins. He says that antioxidants in high doses may do the body harm;

in other cases they may help. We simply don't know yet which ones do which

and when.

" It's a very complicated story, " he says.

You know many antioxidants by name, whether you take them or not: vitamins C

and E, beta carotene and selenium are just the most common. Their purported

health benefits adorn the packaging for everything from cereals to

cosmetics. One can easily walk through the aisles of any grocery, drug or

vitamin store thinking that antioxidants are scientifically validated wonder

pills. They're not, " although the data don't seem to make any difference to

the sales of supplements, " says Veech, chief of the Laboratory of

Membrane Biochemistry at the National Institute on Alcohol Abuse and

Alcoholism, who has reported on the interplay of free radicals and

antioxidants for more than 30 years.

Americans spent $31 billion on vitamin supplements in 1999, according to the

U.S. General Accounting Office. Nearly $2 billion of that was for vitamins E

and C, beta carotene and selenium, according to Nutrition Business Journal.

Up to 30 percent of the population is taking antioxidant supplements

regularly, according to the American Heart Association.

While the efficacy of antioxidant supplements remains gospel in the

health-marketing community, Bortz says the accumulating scientific record

does not verify it. For every study that shows benefits, he says, there is

another study that doesn't.

So with antioxidants and free radicals now seen as playing dual roles of

good guys and bad guys, just what exactly is the state of antioxidant

research? And what health claims can you believe? The experts -- you were

about to guess this -- have a variety of opinions.

Armor All for the Body

It's generally recognized that antioxidants have the ability to serve as

sort of a rust protector for the body, putting a stop to a process called

oxidation.

Important molecules in the body, such as those that form the walls of

arteries, become oxidized when they lose an electron. Once oxidized, they

become unstable and easily break apart.

The culprit, without a doubt, is the free radical, Veech says. Free radicals

are highly reactive molecules, or single atoms with unpaired electrons,

looking for a mate. So they steal an electron from the first thing they

encounter, perhaps a cell wall or a strand of DNA. As free-radical damage

mounts, cells can no longer perform properly. Tissues degrade. Disease sets

in. An excess of free radicals has been cited in the development of

cardiovascular disease, Alzheimer's disease, Parkinson's disease and cancer.

Aging itself

has been defined as a gradual accumulation of free radical damage.

Yet not all free radicals are bad. In fact, free radicals are necessary for

life, according to Britton Chance, professor emeritus of biophysics,

physical chemistry and radiologic physics at the University of Pennsylvania,

a renowned expert on free-radical production. The body cannot turn air and

food into chemical energy without a chain reaction of free radicals, for

instance. Free radicals are also a crucial part of the immune system,

floating through the veins and attacking foreign invaders. They help fight

against bacteria.

Without free radicals, says Chance, " we couldn't have this conversation. "

Free radicals are a natural byproduct of breathing; antioxidants mop some of

them up. A balancing act emerges, says Veech. The body hopes to avoid

excessive free-radical production, but it certainly doesn't want to get rid

of all of them.

A diet rich in fruit, vegetables, nuts and some meats supplies most people

with the antioxidants needed to walk this tightrope, according to a report

last year from the Institute of Medicine. The IOM could find no convincing

evidence that the bulk of the American population needs additional armaments

in the form of antioxidant supplements to fight free-radical damage. The

very notion that free radicals, produced naturally, are some type of

unwelcome houseguest is silly, according to Veech.

Veech says that free radicals have been incorporated into the functioning

human system over millions of years of evolution. The idea that they should

be wiped out or minimized is nonsense, he says.

" God, " he says, " is no fool. "

Low Levels, High Levels

Studies indicate fairly consistently that having too few antioxidants is a

bad thing. One study, published in 1983 in the British medical journal The

Lancet, found that people with low blood levels of selenium were twice as

likely to develop cancer compared with people with normal levels. Another

study, published in 1986 in the New England Journal of Medicine (NEJM),

found that patients with a certain type of lung cancer were four times more

likely to be deficient in beta carotene than a control group.

A 1989 study from the Netherlands associated low selenium levels with an

increased risk of heart attacks. More convincingly, the Harvard-based

Physicians Health Study -- which has recorded the lifestyles of some 50,000

male health professionals for the past 15 years -- found that men who ate a

diet rich in vitamin E (from nuts, seeds and soybeans) were half as likely

to develop heart disease as those with very low levels of dietary vitamin E.

Although these epidemiological studies suggest an association between

antioxidants and good health, this does not mean that the antioxidants

caused the improved health. Nor does it imply that taking antioxidants in a

pill form improves health. In the studies cited above, it is not clear what

is responsible for the lower levels of the nutrients -- a poor diet, a

certain environment, some unknown metabolic factor.

Taking generous doses of antioxidant supplements showed some promise in

studies published in the mid-1990s. Skin cancer patients given daily

selenium supplements were twice as likely to survive their cancer as those

patients not given selenium, the Journal of the American Medical Association

(JAMA) reported in 1996. This was a multi-center, double-blind, randomized,

placebo-controlled study with more than 1,300 patients -- all the markings

of good science. The findings were so dramatic, wrote the authors, that they

stopped the study after six years so that all patients could benefit from

the selenium supplement.

Other studies showed similar positive results: Vitamin E postponed the onset

of debilitating Alzheimer's symptoms in a small study published in the NEJM

in 1997; slowed the progress of coronary artery disease in a study at the

University of Southern California School of Medicine that was published in

JAMA in 1995; cut the risk of cataracts by half in a 1998 Stony Brook (N.Y.)

Medical Center study published in the journal Ophthalmology; and lowered the

risk of prostate cancer in a 1994 NEJM article. Vitamin C helped stave off

blindness, kidney failure and the need for amputation among diabetics,

according to a 1998 Duke University Medical Center report. Extra selenium, a

mineral needed only in trace quantities, reduced the risk of prostate,

colorectal and lung cancer, according to the National Institutes of Health's

Clinical Center (as reported in 1997 and 1998 in journals such as the

American Journal of Epidemiology, Cancer Prevention and Nutrition Review).

Consumers tuned in to these results. Sales of vitamin E grew from $590

million to $860 million from 1995 to 1999, according to Nutrition Business

Journal. Sales of other antioxidants climbed by millions of dollars as well.

But the story doesn't end there. Side by side, over the years, came a wave

of neutral and even negative reports about the benefits of antioxidant

supplements. One study, reported in NEJM in 1994, found that Finnish male

smokers were 18 percent more likely to develop lung cancer after taking a

beta carotene supplement. In 1997, The Lancet published a study of nearly

2,000 men receiving vitamin E, beta carotene, both or a placebo after

suffering their first heart attack. The two beta carotene groups were about

twice as likely to die from a second heart attack or heart disease as the

placebo group, and the vitamin E-only group was about 1.5 times as likely to

die.

Other studies showed similar negative results: no evidence that vitamins C

and E or beta carotene prevented colorectal cancer; no evidence that these

" big three " prevented arteries from re-clogging after angioplasty; no

evidence that beta carotene prevented cancer or heart disease in more than

22,000 physicians over 12 years; no evidence that extra selenium prevented

cancer in 60,000 nurses; and more bad news for smokers taking beta carotene,

this time with a 28 percent higher incidence of lung cancer. These studies

were reported in NEJM from 1994 to 1997.

Criticisms naturally flowed back and forth, with the pro-supplement camp

finding methodological errors in studies casting doubt on pills, and the

anti-supplement folks finding similar problems in the work that seemed to

contradict their findings. .

Strangely, Veech says, all these studies might be absolutely right, pointing

to the complex heart of the matter -- that we don't understand the intricate

relationship between certain types of antioxidants and certain types of free

radicals at different moments over the course of one's lifetime.

" You can't talk about antioxidants en masse, " says Veech. " They all have

different potentials. "

The Antioxidant Paradox

Barry Halliwell of the National University in Singapore wrote a short

article in The Lancet last year entitled " The Antioxidant Paradox. "

Halliwell was lamenting the fact that although diets rich in antioxidants

seem to have a positive effect on health, popping antioxidant supplements

can be either beneficial or harmful, and the results are not at all

predictable.

If the chemistry is all the same (that is, pairing up free electrons and

converting free radicals to neutral molecules), why would a given

antioxidant have different effects at different times on different regions

of the body? Several entirely different mechanisms might be taking place,

researchers say:

• Extra amounts of antioxidants might be turning into pro-oxidants (which

promote the removal of electrons from atoms), fueling free-radical

production and its damage.

• Supplements might do nothing at all because they can't get to where they

are needed.

• Or antioxidants might not be the magic beneficial chemical in the food we

eat after all.

Can antioxidants turn on you? Several studies have shown that people who did

not get the daily recommended allowance of vitamin C had an increase in

free-radical damage to their DNA. But, paradoxically, people who took

megadoses of C also had an increase in DNA damage. The second scenario might

happen, Halliwell says, because vitamin C can worsen cell damage once it has

already started.

Within a cell, certain metal compounds are released as a result of

free-radical damage. These metals themselves can act as a catalyst for

further free-radical damage when they are in a " reduced " state, with a

missing oxygen or extra hydrogen atom. Antioxidants place metals in this

reduced state. Thus, in this environment, antioxidants become pro-oxidants,

Halliwell says.

This was demonstrated in laboratory animals exposed to the pesticide

paraquat, a known carcinogen. Animals that received vitamin C before

exposure were largely protected from cancer. Animals that received vitamin C

after exposure didn't fare so well: The antioxidant aggravated the damage

caused by the herbicide and led to more cancers.

The American Cancer Society (ACS) advises cancer patients not to prescribe

themselves antioxidants because of this potential effect, although it has

never been demonstrated convincingly in human studies.

" Think of antioxidants as drugs, " says Thun, who heads

epidemiological research for the ACS in Atlanta. There are gaps in our

understanding, Thun says, and " antioxidants are not necessarily safe or

beneficial. "

Compounding this is the fact that free radicals can kill cancer cells;

that's how some cancer treatment works. And rapidly multiplying cancer cells

can use antioxidants to their advantage to fuel their growth, Thun says. So

taking antioxidants at the wrong time essentially arms the bad guy with the

weapons to stay alive and multiply.

We should point out that none of this has convinced some practitioners of

alternative medicine not to prescribe antioxidants for cancer. Many do, and

insist mainstream medicine is depriving patients of valuable cures and

treatments.

Another baffling complication is that -- despite the assurances of pill

makers who advise simply taking their pills by mouth and feeling confident

that the body will know what to do with them -- no one knows how to get

antioxidants to travel where they are needed, when they are needed.

Most free-radical damage occurs in the mitochondria, according to the

University of Pennsylvania's Chance. The process of making energy in the

mitochondria, called the respiratory chain, depends on the availability of

free radicals. And extra free radicals are made in the process.

The mitochondria house a tiny, circular strain of DNA that contains 30

genes. This is separate from the double-helix DNA in the cell's nucleus. The

mitochondrial DNA, called mDNA, is often the free radical's first point of

attack. When mDNA is damaged, it cannot do its job of creating the proteins

(molecular messengers) needed for daily bodily maintenance.

This is where a magic bullet could come in handy, Chance says -- something

that could penetrate the mitochondria and mop up a rogue free radical set on

doing damage, while steering clear of the intricate respiratory chain. Yet

mitochondria are veritable fortresses with tough outer walls, moat-like

inner barriers and meandering inner walls protecting their precious

contents. Proteins get out, but antioxidants have a tough time getting in.

" This is where the problem is, " Harmon says, " getting into the

mitochondria. "

No one is sure whether brute force -- which is to say, a megadose of

antioxidants -- is the way into the mitochondria, says Bortz, who was a

colleague of Linus ing, the Nobel laureate who recommended megadoses of

vitamin C to ward off colds, flus and even cancer. Perhaps the body has more

subtle ways of permitting entry.

Diet Vs. Supplements

And so it is that doctors are split on whether to recommend antioxidant

supplements to their patients. The camps are broken down into those who

believe there are not enough data to make blanket recommendations; those who

feel that Americans (particularly children) have such a poor diet that they

need a supplement to ensure adequate levels for basic function; and those

who say that anyone can benefit from increased antioxidants regardless of

how healthy the diet is. A smaller camp sees in the reports about negative

effects of antioxidant pills reason enough not to take any.

For Bortz, who is in his sixties and runs a marathon once a year, whether or

not to take an antioxidant supplement is " an intellectual issue. "

" Anything that will work, I'm for, " Bortz says. " I just don't want people

spending their money on false hopes. . . . Exercise is the master therapy. "

Bortz says " maybe " to vitamin E; " nah " to vitamin C; and " no way " to beta

carotene.

Halliwell argues that a varied diet seems to be more healthy than simple

supplement-taking because the isolated antioxidant might not be the

superhero. Fruit and vegetables are rich in antioxidants, but these plants

contain hundreds of other chemicals. Any single chemical or combination of

chemicals might pack the therapeutic punch.

Nutrients from food enable the body to make its own antioxidants. Veech says

that a chemical produced by the body called glutathione is ultimately

responsible for neutralizing free radicals, and the glutathione

concentration in cells dwarfs that of the free-radical scavengers such as

vitamin C and E. So diet and energy demands determine the amount of free

radical generation and removal, with supplements playing a minuscule role,

if any.

" The production of free radicals, absent genetic defects, results from

normal metabolic processes, " says Veech. " Likewise, the destruction of free

radicals in a non-harmful manner is also the result of normal metabolic

processes.

" People don't want to exercise. They don't want to eat healthy food. They

don't want to stop drinking; they don't want to stop smoking; they don't

want to stop having dangerous sex. They want to take a pill. Well, good

luck. "

Resources

• NIH Clinical Center: www.cc.nih.gov/ccc/supplements/

• NIH Office of Dietary Supplements: dietary-supplements.info.nih.gov/

• FDA Guide to Dietary Supplements:

www.fda.gov/fdac/features/1998/598_guid.html

© 2001 The Washington Post Company

------------------------------------------------------------------------

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Guest guest

MM,

One can test ones free radical output via urine tests.

Those who are optimal likely not need supplement more.

Those who are low should avoid or reduce antioxidant

supplementation. Those who are high should first

try, within reason, to minimize exogenous oxidant exposure.

Then one should add many varied colored

fruits, veggies, herbs,spices, green tea and such.

If retesting shows continued high levels, or if dietary

change is difficult for whatever reason, super green food

formulas (see Super Food Wellness) are really just " fast food health food "

and full of antioxidants too numerous to mention and all still not

discovered!

Then, if still needed, based on test results, supplemental antioxidants,

like Vit E, mixed w/ tocotrionols, or antioxidant multis

(see Antioxidant Optimizer)can slowly be added and

subsequently re-tested. This is not a fool proof method, but certainly

beats the shot gun approach..

Pharmasan.com has the urine test for doctors to order.

A less expensive, though less accurate, OTC

test kit of 4 tests is available in the RxforWellness site.

This allows easy retesting of results.

http://www.rxforwellness.com/shoppingchannel/hormoneantioxidanttestp_9.shtml

The topic is discussed more fully in Vol 1, lesson 1 of the

free antiaging course online . Also see the article archives in the

Foundational AntiAging section.

I can tell you as a practitioned of applied kenesiology that synthetic

antioxidants do not give a positive tetst anywhere near as often as

super food formulas.

Vitally yours,

Dr. H. Maher, ABAAHP

Editor, " Longevity News "

subscribe@...

www.RxforWellness.com

" Your FREE AntiAging prescription Online! "

---- Original Message -----

From: " Mambo Mambo " <mambomambo@...>

<longevity >

Sent: Wednesday, August 08, 2001 11:41 AM

Subject: Re: antioxidants and tumors

> Hello all, a recent article that questions antioxidant mantra:

>

>

> Special to The Washington Post

> Tuesday, August 7, 2001; Page HE01

>

>

> It used to be so simple, a battle between good and evil.

>

> Rogue chemicals called free radicals roam about the body like brazen

street

> punks, the story went, smashing cellular walls and roughing up innocent

DNA

> molecules, causing cancers and the diseases of middle and old age.

>

> Their flagrant disregard for the law would continue unchecked if it

weren't

> for swashbuckling antioxidants swooping in on the wings of dietary

> supplements, disarming the free radicals of their menacing electrons and

> converting them into respectable molecular citizens.

>

> At least that's how the theory went. And the public bought it -- both the

> story and millions of doses of antioxidant supplements, which they

believed

> would reduce disease, boost system performance and maybe even slow the

aging

> clock. But as a bewildering cascade of contradictory, inconclusive and

> outright negative research reports over the past several years suggests,

the

> human body isn't governed by a B-movie script. The antioxidant story isn't

> as simple as some -- largely, those who make and sell them -- would have

us

> believe.

>

> " Free radicals are as good as they are bad, " says Walter Bortz of Stanford

> University Medical School. He is a past president of the American

Geriatric

> Society and author of several popular books on aging and scientific

articles

> on vitamins. He says that antioxidants in high doses may do the body harm;

> in other cases they may help. We simply don't know yet which ones do which

> and when.

>

> " It's a very complicated story, " he says.

>

> You know many antioxidants by name, whether you take them or not: vitamins

C

> and E, beta carotene and selenium are just the most common. Their

purported

> health benefits adorn the packaging for everything from cereals to

> cosmetics. One can easily walk through the aisles of any grocery, drug or

> vitamin store thinking that antioxidants are scientifically validated

wonder

> pills. They're not, " although the data don't seem to make any difference

to

> the sales of supplements, " says Veech, chief of the Laboratory of

> Membrane Biochemistry at the National Institute on Alcohol Abuse and

> Alcoholism, who has reported on the interplay of free radicals and

> antioxidants for more than 30 years.

>

> Americans spent $31 billion on vitamin supplements in 1999, according to

the

> U.S. General Accounting Office. Nearly $2 billion of that was for vitamins

E

> and C, beta carotene and selenium, according to Nutrition Business

Journal.

> Up to 30 percent of the population is taking antioxidant supplements

> regularly, according to the American Heart Association.

>

> While the efficacy of antioxidant supplements remains gospel in the

> health-marketing community, Bortz says the accumulating scientific record

> does not verify it. For every study that shows benefits, he says, there is

> another study that doesn't.

>

> So with antioxidants and free radicals now seen as playing dual roles of

> good guys and bad guys, just what exactly is the state of antioxidant

> research? And what health claims can you believe? The experts -- you were

> about to guess this -- have a variety of opinions.

> Armor All for the Body

>

>

> It's generally recognized that antioxidants have the ability to serve as

> sort of a rust protector for the body, putting a stop to a process called

> oxidation.

>

> Important molecules in the body, such as those that form the walls of

> arteries, become oxidized when they lose an electron. Once oxidized, they

> become unstable and easily break apart.

>

> The culprit, without a doubt, is the free radical, Veech says. Free

radicals

> are highly reactive molecules, or single atoms with unpaired electrons,

> looking for a mate. So they steal an electron from the first thing they

> encounter, perhaps a cell wall or a strand of DNA. As free-radical damage

> mounts, cells can no longer perform properly. Tissues degrade. Disease

sets

> in. An excess of free radicals has been cited in the development of

> cardiovascular disease, Alzheimer's disease, Parkinson's disease and

cancer.

> Aging itself

>

> has been defined as a gradual accumulation of free radical damage.

>

> Yet not all free radicals are bad. In fact, free radicals are necessary

for

> life, according to Britton Chance, professor emeritus of biophysics,

> physical chemistry and radiologic physics at the University of

Pennsylvania,

> a renowned expert on free-radical production. The body cannot turn air and

> food into chemical energy without a chain reaction of free radicals, for

> instance. Free radicals are also a crucial part of the immune system,

> floating through the veins and attacking foreign invaders. They help fight

> against bacteria.

>

> Without free radicals, says Chance, " we couldn't have this conversation. "

>

> Free radicals are a natural byproduct of breathing; antioxidants mop some

of

> them up. A balancing act emerges, says Veech. The body hopes to avoid

> excessive free-radical production, but it certainly doesn't want to get

rid

> of all of them.

>

> A diet rich in fruit, vegetables, nuts and some meats supplies most people

> with the antioxidants needed to walk this tightrope, according to a report

> last year from the Institute of Medicine. The IOM could find no convincing

> evidence that the bulk of the American population needs additional

armaments

> in the form of antioxidant supplements to fight free-radical damage. The

> very notion that free radicals, produced naturally, are some type of

> unwelcome houseguest is silly, according to Veech.

>

> Veech says that free radicals have been incorporated into the functioning

> human system over millions of years of evolution. The idea that they

should

> be wiped out or minimized is nonsense, he says.

>

> " God, " he says, " is no fool. "

> Low Levels, High Levels

>

>

> Studies indicate fairly consistently that having too few antioxidants is a

> bad thing. One study, published in 1983 in the British medical journal The

> Lancet, found that people with low blood levels of selenium were twice as

> likely to develop cancer compared with people with normal levels. Another

> study, published in 1986 in the New England Journal of Medicine (NEJM),

> found that patients with a certain type of lung cancer were four times

more

> likely to be deficient in beta carotene than a control group.

>

> A 1989 study from the Netherlands associated low selenium levels with an

> increased risk of heart attacks. More convincingly, the Harvard-based

> Physicians Health Study -- which has recorded the lifestyles of some

50,000

> male health professionals for the past 15 years -- found that men who ate

a

> diet rich in vitamin E (from nuts, seeds and soybeans) were half as likely

> to develop heart disease as those with very low levels of dietary vitamin

E.

>

> Although these epidemiological studies suggest an association between

> antioxidants and good health, this does not mean that the antioxidants

> caused the improved health. Nor does it imply that taking antioxidants in

a

> pill form improves health. In the studies cited above, it is not clear

what

> is responsible for the lower levels of the nutrients -- a poor diet, a

> certain environment, some unknown metabolic factor.

>

> Taking generous doses of antioxidant supplements showed some promise in

> studies published in the mid-1990s. Skin cancer patients given daily

> selenium supplements were twice as likely to survive their cancer as those

> patients not given selenium, the Journal of the American Medical

Association

> (JAMA) reported in 1996. This was a multi-center, double-blind,

randomized,

> placebo-controlled study with more than 1,300 patients -- all the markings

> of good science. The findings were so dramatic, wrote the authors, that

they

> stopped the study after six years so that all patients could benefit from

> the selenium supplement.

>

> Other studies showed similar positive results: Vitamin E postponed the

onset

> of debilitating Alzheimer's symptoms in a small study published in the

NEJM

> in 1997; slowed the progress of coronary artery disease in a study at the

> University of Southern California School of Medicine that was published in

> JAMA in 1995; cut the risk of cataracts by half in a 1998 Stony Brook

(N.Y.)

> Medical Center study published in the journal Ophthalmology; and lowered

the

> risk of prostate cancer in a 1994 NEJM article. Vitamin C helped stave off

> blindness, kidney failure and the need for amputation among diabetics,

> according to a 1998 Duke University Medical Center report. Extra selenium,

a

> mineral needed only in trace quantities, reduced the risk of prostate,

> colorectal and lung cancer, according to the National Institutes of

Health's

> Clinical Center (as reported in 1997 and 1998 in journals such as the

> American Journal of Epidemiology, Cancer Prevention and Nutrition Review).

>

> Consumers tuned in to these results. Sales of vitamin E grew from $590

> million to $860 million from 1995 to 1999, according to Nutrition Business

> Journal. Sales of other antioxidants climbed by millions of dollars as

well.

>

> But the story doesn't end there. Side by side, over the years, came a wave

> of neutral and even negative reports about the benefits of antioxidant

> supplements. One study, reported in NEJM in 1994, found that Finnish male

> smokers were 18 percent more likely to develop lung cancer after taking a

> beta carotene supplement. In 1997, The Lancet published a study of nearly

> 2,000 men receiving vitamin E, beta carotene, both or a placebo after

> suffering their first heart attack. The two beta carotene groups were

about

> twice as likely to die from a second heart attack or heart disease as the

> placebo group, and the vitamin E-only group was about 1.5 times as likely

to

> die.

>

> Other studies showed similar negative results: no evidence that vitamins C

> and E or beta carotene prevented colorectal cancer; no evidence that these

> " big three " prevented arteries from re-clogging after angioplasty; no

> evidence that beta carotene prevented cancer or heart disease in more than

> 22,000 physicians over 12 years; no evidence that extra selenium prevented

> cancer in 60,000 nurses; and more bad news for smokers taking beta

carotene,

> this time with a 28 percent higher incidence of lung cancer. These studies

> were reported in NEJM from 1994 to 1997.

>

> Criticisms naturally flowed back and forth, with the pro-supplement camp

> finding methodological errors in studies casting doubt on pills, and the

> anti-supplement folks finding similar problems in the work that seemed to

> contradict their findings. .

>

> Strangely, Veech says, all these studies might be absolutely right,

pointing

> to the complex heart of the matter -- that we don't understand the

intricate

> relationship between certain types of antioxidants and certain types of

free

> radicals at different moments over the course of one's lifetime.

>

> " You can't talk about antioxidants en masse, " says Veech. " They all have

> different potentials. "

> The Antioxidant Paradox

>

>

> Barry Halliwell of the National University in Singapore wrote a short

> article in The Lancet last year entitled " The Antioxidant Paradox. "

> Halliwell was lamenting the fact that although diets rich in antioxidants

> seem to have a positive effect on health, popping antioxidant supplements

> can be either beneficial or harmful, and the results are not at all

> predictable.

>

> If the chemistry is all the same (that is, pairing up free electrons and

> converting free radicals to neutral molecules), why would a given

> antioxidant have different effects at different times on different regions

> of the body? Several entirely different mechanisms might be taking place,

> researchers say:

>

> . Extra amounts of antioxidants might be turning into pro-oxidants (which

> promote the removal of electrons from atoms), fueling free-radical

> production and its damage.

>

> . Supplements might do nothing at all because they can't get to where they

> are needed.

>

> . Or antioxidants might not be the magic beneficial chemical in the food

we

> eat after all.

>

> Can antioxidants turn on you? Several studies have shown that people who

did

> not get the daily recommended allowance of vitamin C had an increase in

> free-radical damage to their DNA. But, paradoxically, people who took

> megadoses of C also had an increase in DNA damage. The second scenario

might

> happen, Halliwell says, because vitamin C can worsen cell damage once it

has

> already started.

>

> Within a cell, certain metal compounds are released as a result of

> free-radical damage. These metals themselves can act as a catalyst for

> further free-radical damage when they are in a " reduced " state, with a

> missing oxygen or extra hydrogen atom. Antioxidants place metals in this

> reduced state. Thus, in this environment, antioxidants become

pro-oxidants,

> Halliwell says.

>

> This was demonstrated in laboratory animals exposed to the pesticide

> paraquat, a known carcinogen. Animals that received vitamin C before

> exposure were largely protected from cancer. Animals that received vitamin

C

> after exposure didn't fare so well: The antioxidant aggravated the damage

> caused by the herbicide and led to more cancers.

>

> The American Cancer Society (ACS) advises cancer patients not to prescribe

> themselves antioxidants because of this potential effect, although it has

> never been demonstrated convincingly in human studies.

>

> " Think of antioxidants as drugs, " says Thun, who heads

> epidemiological research for the ACS in Atlanta. There are gaps in our

> understanding, Thun says, and " antioxidants are not necessarily safe or

> beneficial. "

>

> Compounding this is the fact that free radicals can kill cancer cells;

> that's how some cancer treatment works. And rapidly multiplying cancer

cells

> can use antioxidants to their advantage to fuel their growth, Thun says.

So

> taking antioxidants at the wrong time essentially arms the bad guy with

the

> weapons to stay alive and multiply.

>

> We should point out that none of this has convinced some practitioners of

> alternative medicine not to prescribe antioxidants for cancer. Many do,

and

> insist mainstream medicine is depriving patients of valuable cures and

> treatments.

>

> Another baffling complication is that -- despite the assurances of pill

> makers who advise simply taking their pills by mouth and feeling confident

> that the body will know what to do with them -- no one knows how to get

> antioxidants to travel where they are needed, when they are needed.

>

> Most free-radical damage occurs in the mitochondria, according to the

> University of Pennsylvania's Chance. The process of making energy in the

> mitochondria, called the respiratory chain, depends on the availability of

> free radicals. And extra free radicals are made in the process.

>

> The mitochondria house a tiny, circular strain of DNA that contains 30

> genes. This is separate from the double-helix DNA in the cell's nucleus.

The

> mitochondrial DNA, called mDNA, is often the free radical's first point of

> attack. When mDNA is damaged, it cannot do its job of creating the

proteins

> (molecular messengers) needed for daily bodily maintenance.

>

> This is where a magic bullet could come in handy, Chance says -- something

> that could penetrate the mitochondria and mop up a rogue free radical set

on

> doing damage, while steering clear of the intricate respiratory chain. Yet

> mitochondria are veritable fortresses with tough outer walls, moat-like

> inner barriers and meandering inner walls protecting their precious

> contents. Proteins get out, but antioxidants have a tough time getting in.

>

> " This is where the problem is, " Harmon says, " getting into the

> mitochondria. "

>

> No one is sure whether brute force -- which is to say, a megadose of

> antioxidants -- is the way into the mitochondria, says Bortz, who was a

> colleague of Linus ing, the Nobel laureate who recommended megadoses

of

> vitamin C to ward off colds, flus and even cancer. Perhaps the body has

more

> subtle ways of permitting entry.

> Diet Vs. Supplements

>

>

> And so it is that doctors are split on whether to recommend antioxidant

> supplements to their patients. The camps are broken down into those who

> believe there are not enough data to make blanket recommendations; those

who

> feel that Americans (particularly children) have such a poor diet that

they

> need a supplement to ensure adequate levels for basic function; and those

> who say that anyone can benefit from increased antioxidants regardless of

> how healthy the diet is. A smaller camp sees in the reports about negative

> effects of antioxidant pills reason enough not to take any.

>

> For Bortz, who is in his sixties and runs a marathon once a year, whether

or

> not to take an antioxidant supplement is " an intellectual issue. "

>

> " Anything that will work, I'm for, " Bortz says. " I just don't want people

> spending their money on false hopes. . . . Exercise is the master

therapy. "

>

> Bortz says " maybe " to vitamin E; " nah " to vitamin C; and " no way " to beta

> carotene.

>

> Halliwell argues that a varied diet seems to be more healthy than simple

> supplement-taking because the isolated antioxidant might not be the

> superhero. Fruit and vegetables are rich in antioxidants, but these plants

> contain hundreds of other chemicals. Any single chemical or combination of

> chemicals might pack the therapeutic punch.

>

> Nutrients from food enable the body to make its own antioxidants. Veech

says

> that a chemical produced by the body called glutathione is ultimately

> responsible for neutralizing free radicals, and the glutathione

> concentration in cells dwarfs that of the free-radical scavengers such as

> vitamin C and E. So diet and energy demands determine the amount of free

> radical generation and removal, with supplements playing a minuscule role,

> if any.

>

> " The production of free radicals, absent genetic defects, results from

> normal metabolic processes, " says Veech. " Likewise, the destruction of

free

> radicals in a non-harmful manner is also the result of normal metabolic

> processes.

>

> " People don't want to exercise. They don't want to eat healthy food. They

> don't want to stop drinking; they don't want to stop smoking; they don't

> want to stop having dangerous sex. They want to take a pill. Well, good

> luck. "

> Resources

>

>

> . NIH Clinical Center: www.cc.nih.gov/ccc/supplements/

>

> . NIH Office of Dietary Supplements: dietary-supplements.info.nih.gov/

>

> . FDA Guide to Dietary Supplements:

> www.fda.gov/fdac/features/1998/598_guid.html

>

>

> © 2001 The Washington Post Company

>

>

>

> ------------------------------------------------------------------------

>

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