Free Radicals and Antioxidants: Their Role in the Prevention, Management & Treatment of Disease

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FREE RADICALS AND ANTIOXIDANTS: THEIR ROLE JoAnn Guest Feb 07, 2004 19:12

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FREE RADICALS AND ANTIOXIDANTS:

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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

apa-

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JoAnn Guest

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