Free Radicals and Antioxidants: More than a Case of Bad Guys and Good Guys

[Guest guest]

FREE RADICALS AND ANTIOXIDANTS:

MORE THAN A CASE OF BAD GUYS AND GOOD GUYS

 

THEIR ROLE IN THE PREVENTION, MANAGEMENT

AND TREATMENT OF DISEASE

by Andreas M. Papas M.Sc., Ph.D. President YASOO Health Inc.

Adjunct Professor, James Quillen College of Medicine, East Tennessee State

University, Johnson City, TN

Senior Scientific Advisor, The Cancer Prevention Institute, Harvard University

 

INTRODUCTION

http://www.willner.com/References/PappasFreeRadicals.htm

 

Most of us view free radicals and antioxidants as a classic case of bad guys the

free radicals, and good guys the antioxidants. While this understanding may be

rather simplistic, significant research indicates that management of the

production of free radicals and effective use of antioxidants can provide useful

tools for the prevention, management and treatment of disease.

 

FREE RADICALS—THE BAD GUYS?

Atoms consist of the positively charged nucleus and negatively charged

electrons. Electrons orbit around the nucleus in pairs. When an electron from a

pair is removed the molecule becomes very unstable. A free radical is any

chemical species, capable of independent existence with one or more unpaired

electrons. Free radicals with major biological significance include superoxide,

hydroxyl, lipid, nitric oxide, thiyl and protein radicals. Scientists group with

free radicals non-radical compounds that are strong oxidants or can be converted

easily to free radicals. Some examples include hydrogen peroxide, singlet oxygen

and ozone.

Free radicals are extremely reactive. The half-life of one of the most damaging

free radicals, the hydroxyl radical, is one billionth of a second. This means

that it will attack the first molecule in its path fat, protein, DNA, sugar and

‘steal’ electrons. This process, called oxidation, is the same process that

causes our cars to rust and slices of apple to turn brown and may have major

impact on aging and health and disease.

 

Free radicals are part of life

 

Free radicals are produced in every tissue of our body. Three major sources of

free radicals are:

The mitochondria. We use oxygen to oxidize glucose in the mitochondria to

produce energy as ATP (adenosine triphosphate). Even under normal conditions,

electrons deviate from their normal path and combine with oxygen or other

molecules to form free radicals. Excess production of free radicals ruptures the

membrane of the mitochondria and opens the floodgates of free radicals.

 

Lipid oxidation. Lipid material in our body plays critical role in membranes,

LDL, hormones, and many tissues including nerve tissue. Lipids, especially

polyunsaturated fatty acids are prone to oxidation. Oxidation of a single lipid

molecule by a single radical can start a chain reaction, which can oxidize all

lipid material.

 

The immune system. Free radicals are formidable weapons in the arsenal of our

immune system. The phagocytes produce free radicals and use them to kill

invading bacteria and viruses.

Do free radicals have any other redeeming value? The answer is yes. The singlet

oxygen and nitric oxide (NO) play a very important role in regulating cell

growth and cell to cell communication. NO dilates blood vessels and lowers blood

pressure (the 1998 Nobel Prize in Medicine was awarded for the research on the

role of NO).

Free radicals are important part of our metabolism and do have useful functions.

It is the excessive production of free radicals at the wrong time and place that

causes harmful oxidative stress.

 

FREE RADICALS IMPLICATED IN AGING AND CHRONIC DISEASE

 

Aging: Every major theory on aging assumes a role for free radicals. The free

radical theory hypothesizes that free radicals cause degenerative changes. Free

radicals fit well other major theories of aging such as the telomere,

mitochondrial DNA, glycosylation and immunological theories.

Oxidative stress and chronic disease. Oxidative stress is believed to contribute

to the development of chronic disease including heart disease, cancer, cataracts

and neurodegenerative diseases such as Alzheimer’s.

 

The evidence is rather compelling:

•DNA damage has been associated with development of cancer

•Oxidized LDL appears to contribute significantly to atherosclerosis.

•Nitrogen and lipid radicals have been implicated in the pathogenesis and

progression of neurodegenerative diseases including Alzheimer’s

•Free radicals have been shown to contribute to the development of cataracts in

animal models

•Free radicals have been implicated in the skin damage from photoaging, UV

radiation, ozone and environmental pollutants

•Free radicals contribute significantly to ischemia-reperfusion injury.

 

ANTIOXIDANTSTHE GOOD GUYS?

Antioxidants delay or inhibit oxidative damage in several ways:

•Prevent the formation of excess free radicals.

•Scavenge the free radicals after they are formed before they damage other

molecules.

•Repair damaged molecules or replace them with new ones.

The body’s antioxidant system comprises a number of components, which evolved

over a very long time. It is very important to consider individual antioxidants

as components of a system with major interdependence and interactions. Some

antioxidants are produced in our body (endogenous) while others come from our

diet (exogenous). Important endogenous antioxidants include glutathione,

catalases, NADPH, ubiquinol-10, Mn, Cu, superoxide dismutase (SOD), uric acid,

lipoic acid, and metal binding proteins such as albumin and ferritin. Dietary

and exogenous antioxidants include vitamin E, vitamin C, vitamin A and

carotenoids, Se, phytochemicals with antioxidant activity, and dietary and other

supplements.

 

STRENGTHENING THE BODY’S ANTIOXIDANT SYSTEM

Antioxidant status is the dynamic balance between the antioxidant system and

free radicals. A major imbalance favoring free radicals, known as oxidative

stress, contributes to aging and chronic disease. The antioxidant status is

affected by:

1. Excess production of free radicals, due to a variety of factors including

genetic, dietary, environmental, physiological and emotional factors, UV

radiation, injury, disease, and medications

2. Endogenous production and exogenous supply of antioxidants or from the diet

or supplements.

The objective of intervention is to reduce oxidative stress by reducing the

production of free radicals and strengthening the body’s antioxidant system.

Physicians are faced with serious conditions of oxidative stress, which require

immediate attention. For this reason, I will focus on the use of antioxidants as

part of a long-term comprehensive strategy (including dietary and lifestyle

changes) to support healthy antioxidant status.

 

DEVELOPING THE RIGHT STRATEGY FOR USING ANTIOXIDANTS

Antioxidants work as a system. Supplying a spectrum of effective antioxidants is

more important than megadoses of single antioxidants. There are cases, however,

that due to special needs, higher doses of one antioxidant may be required.

The product chemical form, formulation and bioavailability have major impact on

efficacy and safety. For vitamin E the form used is of critical importance.

Disease conditions, physiological status and medications have a major impact on

absorption, secretion and requirement for antioxidants. Higher dose and special

formulations may be required in the management and treatment of disease and for

different physiological stages such as aging and menopause.

Food versus supplements. While food is by far the preferred source of

antioxidants, supplementation is needed to achieve effective levels for

prevention of disease and wellness and for therapy. For some antioxidants, such

as vitamin E, it is almost impossible to obtain from the food the amounts

believed to be required for prevention of disease and wellness. For most

antioxidants, it is difficult to obtain from the food therapeutic levels.

Safety should be a major consideration. Safety of large doses of antioxidants

becomes a major consideration in specific disease conditions or in people

receiving some specific medications. For example, very large doses of

beta-carotene might be harmful in smokers. The anticoagulant effect of vitamin

E, although minor, must be considered in patients receiving blood-thinning

medications. A possible interaction of large dose of antioxidants on the effect

of Zocor plus niacin therapy on HDL has been suggested in a recent report.

 

SPECIFIC RECOMMENDATIONS

The following recommendations are for consideration by physicians for possible

incorporation in the treatment strategy for their patients..

Healthy individuals (with no family history of chronic disease).

A wide-spectrum antioxidant which supplies vitamin E as natural tocopherols plus

tocotrienols, natural carotenoids (alpha, beta, and gamma-carotene, lutein,

lycopene and astaxanthin), vitamins A and C, CoQ10, alpha-lipoic acid selenium,

zinc, copper and manganese can provide a basic supplement. Inclusion of folic

acid, vitamins B6 and B12, and betaine can enhance its potential due the role of

folic acid in repairing DNA and the role of the combination in reducing

homocysteine, a risk-factor for heart disease.

With increasing age healthy individuals can benefit from additional vitamin E.

The following guidelines may be considered:

 

 

Supplementation Guidelines Based on Age

Age: Below 30—Basic wide-spectrum antioxidant

Age: 30-40 years—Basic wide-spectrum antioxidant plus 100 IU plus 100 mg of

natural tocopherols plus tocotrienols

Age: 40-60 years—Basic wide-spectrum antioxidant plus 400 IU plus 400 mg of

natural tocopherols plus tocotrienols

Age: 60-80 years—Basic wide-spectrum antioxidant plus 400 IU plus 400 mg of

natural tocopherols plus tocotrienols 800 mg tocopherol mixture rich in

gamma-tocopherol

Age: Above 80 years—Basic wide-spectrum antioxidant plus (2X) 400 IU plus 400 mg

of natural tocopherols plus tocotrienols 800 mg tocopherol mixture rich in

gamma-tocopherol (2X)

People with family history of chronic disease and special needs.

Alzheimer’s (and other neurodegenerative diseases?). A major clinical study in a

number of medical centers across the United States found that in Alzheimer’s

patients taking large doses of vitamin E, progression of the disease was delayed

by approximately seven months (N Engl J Med 1997: 336:1216-1222). The American

Psychiatric Association Practice Guidelines recommend use of vitamin E in newly

diagnosed and mildly impaired individuals. Vitamin E has been suggested to be

beneficial in slowing the progression of ALS and to reduce the side effects of

antipsychotic medications. Increasing evidence indicates that a class of

nitrogen radicals may play an important role in these neurodegenerative

diseases. Because gamma-tocopherol appears to be effective in neutralizing these

free radicals, this form of vitamin E is recommended for these conditions.

 

Depending on the risk and the state of the disease the following supplementation

may be considered.

•Basic wide-spectrum antioxidant, plus

•400 IU plus 400 mg of natural tocopherols plus tocotrienols (1-2X), plus

•800 mg tocopherol mixture rich in gamma-tocopherol (1-3X)

 

 

Cancer: In the Finnish (ATBC) study, with over 29,000 elderly male smokers,

those taking vitamin E for six years had 32 percent fewer diagnoses of prostate

cancer and 41 percent fewer prostate cancer deaths than men who did not take

vitamin E. There was also a trend (16%) for reduction in colon cancer (J Natl

Cancer Inst 1998;90:440-446). A study by Johns Hopkins University evaluated the

alpha and gamma-tocopherols and selenium on prostate cancer. For

gamma-tocopherol, men in the highest fifth of blood concentration had a fivefold

reduction in the risk of developing prostate cancer than men in the lowest

fifth. A strong inverse association with selenium supports earlier results of a

clinical study (J Natl Cancer Inst 2000;92:2018-2023). Tocotrienols inhibit

growth of breast cancer cells but clinical data are not available at this time.

Other nutrients with promising potential include folic acid for colon cancer and

lycopene for prostate cancer. Vitamin E appears to increase the

efficacy of the drug 5-fluorouracil. The role of antioxidants in conjunction

with chemotherapy remains controversial.

Depending on the risk and the state of the disease the following supplementation

may be considered.

•Basic wide-spectrum antioxidant (supplies selenium, carotenoids and folic

acid), plus

•800 mg tocopherol mixture rich in gamma-tocopherol for prostate cancer

•400-1200 mg tocotrienol rich extract for breast cancer

 

 

Cataracts and other eye diseases: A number of studies suggest that antioxidant

nutrients and particularly vitamins and C, carotenoids such as beta-carotene,

lutein and zeaxanthin) play a role in the prevention of age-related nuclear lens

opacities (Arch Ophthalmol 2001;119:1009-19). Riboflavin and folic acid appear

to have a protective effect. Initial evidence suggests that antioxidants and

particularly lutein and zeaxanthnin may delay the onset of age-related macular

degeneration.

Depending on the risk the type and state of the disease the following

supplementation may be considered.

•Basic wide-spectrum antioxidant which includes vitamins C and E and natural

carotenoids (2X)

•Additional lutein and vitamin E (100-400 IU plus 100-400 mg of natural

tocopherols plus tocotrienols) may be considered

 

 

Heart disease: Epidemiological studies indicated a strong protective effect of

vitamin E Subsequent large intervention studies (HOPE, GISSI) with high levels

of alpha-tocopherol failed to show the beneficial effect especially in high-risk

This may, at least in part to the use of alpha-tocopherol alone. Recent data

suggest an important role of gamma-tocopherol (J Am Coll Cardiol 1999:1208-1215)

and the tocotrienols. In a 5-year placebo-control study in 50 patients with

previous cerebrovascular disease, a tocotrienol rich extract produced regression

or slowed progression of carotid artery stenosis as measured by ultrasonography.

Those receiving a placebo had an overall worsening of the disease. There was

also improvement in the cholesterol profile. Thus, the form of vitamin E appears

to play a critical role. Other nutrients with very promising benefits include

omega-3 fatty acids and homocysteine reducing compounds such as folic acid (and

other B vitamins) and betaine and CoQ10.

Depending on the risk and other factors the following supplementation may be

considered.

•Basic wide-spectrum antioxidant (supplies CoQ10, folic acid, B12, B6, betaine)

•400-2,000 mg tocotrienol rich extract (contains gamma-tocopherol)

•Omega-3 fatty acids

 

 

Diabetes, liver and kidney diseases. The objective is to help reduce the risk of

complications of diabetes or the worsening of the liver and kidney diseases.

Beneficial effects of vitamin E and antioxidants have been suggested in:

haemodialysis patients with prevalent cardiovascular disease (Lancet

2000;356:1213-; diabetic retinopathy (Diabetes 2001;50:1938-42); and liver

disease (Adv Pharmacol 1997;38:601-2

Depending on the risk and other factors the following supplementation may be

considered.

•Basic wide-spectrum antioxidant

•800 mg tocopherol mixture rich in gamma-tocopherol (1-2X)

 

 

Immunity and diseases associated with inflammation: In the elderly vitamin E

improved delayed-type hypersensitivity skin response (DTH) by 65 percent and

antibody response to hepatitis B six-fold. It also increased significantly the

antibody titer to the tetanus vaccine (JAMA 1997;277:1380-6). Supplementation

with vitamins C and E appears to reduce the severity of asthma (Arch Environ

Health;56: 242-9); glucosamine plus chondroitin, vitamin E, fish oil,

gamma-linoleic acid appear to reduce the severity of arthritis. Because the

gamma-tocopherol form of vitamin E has been shown to have strong

anti-inflammatory

Depending on the individual situation the following supplementation may be

considered.

•Basic wide-spectrum antioxidant (1-2X)

•400 IU plus 400 mg of natural tocopherols plus tocotrienols (for support of the

immune system.

•800 mg tocopherol mixture rich in gamma-tocopherol (1-3X for inflammation

related conditions). Glucosamine plus chondroitin, fish oil and gamma-linoleic

acid may also be used for management of arthritis)

CONCLUSION

Use of antioxidants, based on scientific and clinical evidence, can be used in

clinical practice for the prevention, management and treatment of disease.

 

 

ANDREAS M. PAPAS, Ph.D.

Author of The Vitamin E Factor paperback and editor of the scientific book

Antioxidant Status, Diet, Nutrition and Health, Dr. Papas is President, YASOO

Health Inc. and Adjunct Professor, of the College of Medicine of East Tennessee

State University and Senior Scientific Advisor, Cancer Prevention, Institute

Harvard School of Epidemiology. A Fulbright Scholar, Dr. Papas is a graduate of

the University of Illinois and an expert on vitamin E and antioxidants.

 

 

Correspondence to:

Andreas M. Papas, PhD, President

YASOO Health Inc.

P.O. Box 3608

Johnson City, TN USA 37602-36086

TEL: 423-926-3490

FAX: 423-926-3586

apapas

_________________

JoAnn Guest

mrsjoguest

DietaryTipsForHBP

http://www.geocities.com/mrsjoguest

 

 

 

 

 

 

 

The complete " Whole Body " Health line consists of the " AIM GARDEN TRIO "

Ask About Health Professional Support Series: AIM Barleygreen

 

" Wisdom of the Past, Food of the Future "

 

http://www.geocities.com/mrsjoguest/AIM.html

 

PLEASE READ THIS IMPORTANT DISCLAIMER

We have made every effort to ensure that the information included in these pages

is accurate. However, we make no guarantees nor can we assume any responsibility

for the accuracy, completeness, or usefulness of any information, product, or

process discussed.

 

 

 

 

 

 

 

Finance Tax Center - File online. File on time.