Antioxidants: the big picture

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Antioxidants in Health and Disease: The Big

Picture

 

Antioxidants in Health and Disease: The Big Picture

JoAnn Guest Jun

16, 2005 20:51 PDT

E. Cheraskin, MD, DMD

(Reprinted with permission of the author and the

Journal of

Orthomolecular Medicine 10: #2, 89-96, Second Quarter,

1995.)

Abstract

http://www.doctoryourself.com/antioxidants.html

 

In December, four reports appeared describing the

ecology of macular

degeneration (MD). (1-4) It was generally agreed that

the environmental

contribution includes sunlight. It was suggested that

the antioxidants

serve to counter the oxidative damage. In any case,

the articles

prompted a letter to the editor entitled, " Now That We

Have All The

Pieces... Why Is There Still A Puzzle?” (5) This was

intended to

indicate that we still have very little opportunity to

slow and/or stop

the degenerative process. We have even less knowledge

about how to

reverse and/or prevent MD.

 

This report is intended to cast additional light on

the subject It is

suggested that, viewed in the bigger picture, the

total body concept,

significant changes in macular degeneration and other

diseases may

occur

when larger-than-recommended amounts of the

antioxidants are supplied.

 

Additionally, it is proposed that the therapy be

instituted for longer

periods of time and begun earlier in life. It is hoped

that this report

will continue more action in the pursuit of this

approach to macular

degeneration.

 

Introduction

The literature is replete with information which

suggests that a common

denominator in the aging process and in the major

diseases associated

with aging is oxidative damage.

 

This has led to an interest in the use of antioxidants

in the

prevention and treatment of such problems. There are

hundreds, if not

thousands, of articles on this subject. Some are

retrospective; other

prospective. They deal with large and small samples of

short and long

duration. They range from the womb to the tomb.

 

Most of them are of an epidemiologic (correlational)

nature. However,

many are concerned with intervention and possibly

provide causal data.

 

This report will outline evidence to show that the

antioxidants are

necessary, singly, in combinations, in larger amounts

than generally

held, and must be started much earlier in life.

 

Hence, we will attempt to emphasize the relationship

of antioxidants to

common disorders such as heart disease, cancer,

diabetes, arthritis,

cataracts, and macular degeneration as well as other

syndromes through

an examination of 40 representative studies in the

English language

literature.

 

Vitamin A Studies

Included (Table 1) are five representative studies of

vitamin A

consumption in health and disease. (6-10) According to

the Subcommittee

on Foods and Nutrition of the National Research

Council, the daily

recommended requirements (RDA) for vitamin A are 5,000

and 4,000 IU

respectively for men and women.

 

(11) It is clear from Table 1 that much larger amounts

than proposed

for

healthy people in the RDA are needed. Additionally,

the evidence from

these studies suggest that there were no side effects.

 

 

It is generally recognized that vitamin A blood levels

below 10 mcg%

are

considered evidence of obvious deficiency. (12) Olson

contends that the

normal range is 20 to 50 mcg% and therefore anything

above 50 is high.

 

Table 2 summarizes the studies on vitamin A in the

blood in health and

sickness. You will note that the reports shown suggest

that what Olson

call high levels are probably the desired amounts.

 

Vitamin C Studies

According to the Recommended Dietary Allowances, 60 mg

of vitamin C is

the suggested normal requirement. (11)Table 3 features

studies which

underscore the desirability of larger-than-recommended

amounts. (18-22)

 

 

It will be noted that amounts as large as three grams

per dose provide

remarkable consequences.

 

Back in the '40s, the Interdepartmental Committee on

Nutrition for

National Defense (ICNND) began to set the standards

for optimal plasma

vitamin C. Originally, acceptability was anything

above 0.1 mg%.

Through

the '40s, the figures were changed to 0.2 and then 0.4

mg%.

 

Most of the literature today considers 0.4 mg% as

being a satisfactory

blood vitamin C level. In this connection, Block

points out that 15% of

white men, 65-74 years of age, in the U.S. today have

blood ascorbate

levels below 0.4 mg%.(23) Chandra views 0.5 to 2.0 mg%

as the

acceptable range. (24) It is clear from Table 4 that

the best clinical

results parallel plasma levels above 1.0 mg%. (17,

25-28)

 

Vitamin E Studies

According to the RDA, 30 mg of vitamin E or 10 mg of

alpha tocopherol

is

considered the recommendation for healthy man.(11) It

will be noted

(Table 5) that amounts ranging from 400 to 3200 mgs

contribute to the

solution of many classical problems. (29-33)

 

There is not much in the literature regarding the

optimal blood vitamin

E levels. MachIm, in his book (34) indicates that

anything less than

0.7

mg% is deficient, levels between 0.7 and 0.9 are low,

and values above

0.9 mg% are acceptable.

 

Simonoff adds the fact that the blood levels of

vitamin E are different

in the sexes and at different ages. (35) For example,

in the young

adult, the values should be 1.6 to 1.9 mg% and

decrease with age to 0.9

to 1.1 mg% in the elderly. In the light of these

so-called norms, it is

interesting (Table 6) that salutary effects seem to

parallel higher

blood vitamin E levels. (14, 36-39)

 

 

Other Antioxidants

While vitamins A, C, and E have been recognized for a

long time for

their antioxidant properties, there are others such as

zinc, selenium,

and bioflavinoids which directly or indirectly serve

as free radical

scavengers.

 

Perhaps the one receiving the most attention at the

moment is the

carotenoids and particularly beta carotene. Since beta

carotene serves

as a provitamin A, there are suggestions as to its

daily requirement.

(11) However, beta carotene also serves an independent

function as an

antioxidant. The requirement in this regard is not

very clear.

 

Table 7 outlines the relationship of dietary beta

carotene to some of

our major problems. (40-44)

 

There seems to be no question but that beta carotene

in

larger-than-generally recommended amounts exert

salutary effects.

 

In line with our earlier format, Table 8 outlines the

blood carotene

levels. (14, 45-48) In general, the levels in health

are considerably

larger than those with illness.

 

The Antioxidant Index

Perhaps more importantly is the observation that the

relationship

between various antioxidants in health and disease are

sharpened when

they are viewed as an antioxidant index.

 

For example, macular degeneration, (26) colorectal

adenomas, (49)

rheumatoid arthritis, (50) cancer, (51) and

cardiovascular disease,

(52)

become even more meaningful when viewed in terms of

conditions of

antioxidants rather than single ones.

 

Comments

We have been trying to answer the question of the role

of antioxidants

in the aging process and in age-related diseases. We

think that we have

some of the answers. It would seem, from what has

transpired, that the

antioxidants are important in the prevention and

treatment of these

problems. However, there are still unanswered

questions.

 

We still do not know all of the antioxidants. We are

still not sure of

the dosages except that they are larger than usually

recommended. We

have little information about the amounts for

different diseases. For

example, are the dosages larger for macular

degeneration than heart

disease? Or, are the amounts more a function of the

oxidative damage?

And, perhaps more importantly, we do not have the time

frame period.

 

Since the disturbances associated with aging and these

age-related

diseases are characterized by a long incubation period

and an insidious

clinical course, the question of when one should

institute an

antioxidant program is still unresolved. The one thing

we know for sure

is starting when the disease appears is too late.

 

Summary and Conclusions

In the final analysis, how we fare is a function of

two sets of

interdependent factors. On the one hand, we are at the

mercy of

numerous

environmental threats, such as physical, chemical,

microbial, thermic,

actinic, and psychologic. For macular degeneration,

the dominant one is

solar radiation; for lung cancer, it is tobacco

consumption. However,

how we fare is also a function of how well we tolerate

these

environmental challenges. These protective systems are

collectively

referred to as resistance/susceptibility,

constitution, predisposition,

immunocompetence, homeostasis and/or harmony.

 

The antioxidants serve as an important ingredient in

building

resistance and reducing susceptibility and largely

because of its free

radical scavenging action.

 

However, how much, when and for how long are still the

burning

questions. At the moment, in the light of these 40

representative

studies, macular degeneration and cataracts enjoy

positions like heart

disease and cancer.

 

(Table 1 in the original paper contains Dietary

Vitamin A Levels)

 

Reference # 6/ Precancer

In a study of oral leukoplakia, patients were given

200,000 IU of

vitamin A per week for six months versus placebo

capsules. Fifty-seven

per cent of vitamin A supplemented patients had

complete remission and,

during that time, no new lesions appeared.

 

#7/HIV

A study was done with 25 HIV patients with CD4+ T cell

counts less than

800. Thirty-two per cent of the subjects had retinol

levels less than

30

mcg%. Subjects taking a daily multivitamin containing

modest amounts of

vitamin A (1500-2100 mcg) had higher serum retinol

levels than those

taking no supplements (72 versus 42 mcg%). These

observations suggest

that even modest doses of vitamin A can have

significant impact on

serum

retinol levels in advanced HIV patients.

 

#8/ Cancer

A case control study conducted among a cohort of

chemical manufacturing

employees provided an opportunity to test the

hypothesis that lung

cancer risk is inversely related to dietary intake of

vitamin A.

 

Subjects in the lowest tercile of vitamin A intake

(less than 62,000

lU/week) had approximately twice the risk of lung

cancer as those in

the

highest (greater than 100,000 IUI week).

 

#9/Respiratory Tract Infections

Preschool-age children (157) with a history of

frequent respiratory

illness were randomized into vitamin A supplemented

(450 mcg/day) and

placebo groups. Respiratory symptoms were recorded on

a daily basis

over

a period of 11 months. The children who received the

supplement

experienced 19% fewer episodes of respiratory

symptomatology than their

placebo counterparts.

 

#10/Mortality

Mortality of Sumatran children randomized to receive a

200,000 IU

vitamin A capsule (n=9776) was compared with those who

did not

(n=2447).

During the four months after completion of the first

distribution,

mortality among the recipients was 75 per cent less

than the

nonrecipients. One capsule every six months may

provide adequate

protection for the vast majority of children.

 

(Table 2 in the original paper contains Blood Vitamin

A Levels)

 

Reference # 13/Measles

In a study of children in Long Beach, California, the

blood levels in

youngsters with measles was 24 mcg%; in those with

nonmeasles 26 mcg%;

and in the well kids 40 mcg%.

 

#14/ Alzheimer's Disease

Elderly people with Alzheimer's Disease

post-infarct-dementia and

controls were examined. The average vitamin A levels

were 45 mcg% in

Alzheimer's Disease compared to an average 61 mcg% in

the control

group.

 

 

#15/ Cancer

The vitamin A blood levels of patients with pulmonary

cancer,

non-cancer

pulmonary disease, and controls were compared. The

levels were 45.6

mcg%

(range 20.2 to 79.5) for the pulmonary cancer

subjects; 64.3 mcg%

(range

43.6 to 80.8) for the patients with noncancer

pulmonary disease; and

68.4 mcg% (range 52.6 to 101.2) in the controls.

 

#16/ Bronchopulmonary Disease

This study showed that low vitamin A levels (less than

10 mcg%)

observed

in infants with bronchopulmonary dysplasia (BPD), and

implies that

therapeutic administration of vitamin A may help

prevent and treat BPD.

 

#17/ Cardiovascular Disease

There is data from the cross-cultural European

comparisons of the

Edinburgh Aging Control Study and of the Basel

Prospective Study. They

show, for the first time with fair probability, that

vitamin A

concentrations needed to decrease ischemic heart

disease risk are 63 to

80 mcg%.

 

(Table 3 in the original paper contains Dietary

Vitamin C Levels)

 

Reference #18/Infertility

One gram of ascorbic acid per day for 60 days was

provided to 20

clearly-diagnosed infertile, but otherwise healthy,

men. A separate

control group of 20 men were placebo-supplemented. At

the end of these

two months, conception occurred unanimously only in

the vitamin C

supplemented couples!

 

#19/Diabetes

A study of the small blood vessels of the skin and

retina was carried

out in 24 normal subjects and 12 diabetics. The

experiment revealed

very

clearly that the capillary strength of both the eye

and skin of all

diabetics improved during the vitamin C treatment (one

gram/day) and

worsened when it was discontinued.

 

#20/Mental Illness

The manic/depressive state was assessed in 24 subjects

who completed

two

generally accepted psychometric tests. Each patient

was provided with

either a three gram ascorbic acid effervescent tablet

or a placebo. In

the vitamin C treated group, the severity of the

bipolar state was

reduced within the first hour and then declined even

more rapidly

between the second and fourth hours. No change

occurred in the placebo

subset.

 

#21/Life Expectancy

In a reexamination of a large federal government

study, it was

discovered that those men who consumed 300 to 400 mgs

of vitamin C

daily

compared with those who consumed less than 50 mgs

showed art overall

mortality reduction of 42% principally due to a

decline in heart

disease

and cancer. This translates into living approximately

six years longer!

 

#22/ Cardiovascular Disease

A 1000 mg ascorbic acid tablet or a placebo was

supplemented daily to

20

adults for two six-week periods in a randomized,

crossover design.

Under

these conditions, vitamin C supplementation reduced

the systolic

pressure.

 

(Table 4 in the original paper contains Blood Vitamin

C Levels)

 

Reference #25/Periodontal Disease

In a study of 24 adult volunteers with initially low

and partially even

deficient plasma vitamin C values, the hydroxyproline

and proline

content was measured before and after supplementation.

There was a

statistically significant rise but not before the

plasma ascorbate

level

was above 0.9 mg%. The optimal plasma vitamin C level

which was

associated with the highest hydroxyproline and proline

content in

periodontal tissue ranged between 1.0 and 1.3 mg%.

 

#17/Heart Disease

The most recent work on risk factors in ischemic heart

disease (IHD) is

available from several cross-cultural epidemiologic

studies. They all

suggest, for the first time with fair probability,

that protection

against IHD is paralleled by vitamin C levels in the

range of 0.7 to

0.9

mg%.

 

#26/ Macular Degeneration

From the Eye Disease Case Control Study Group, there

is evidence that

blood levels of vitamin C in the 0.7 to 1.6 mg% range

have a risk of

one

third to one half that in blood levels below 0.7 mg%

for macular

degeneration.

 

#27/ Hypertension

In a study of 685 patients without known hypertension,

it was

discovered

that the higher the plasma vitamin C level, the lower

the systolic and

diastolic pressure. Specifically, with plasma ascorbic

acid (PAA) of

0.7

mg%, the blood pressure was 147/83 mm Hg; with PAA of

1.4 mg%, the

pressure was 139/78 mm Hg.

 

#28/ Cataracts

A classification was designed of three blood ascorbate

levels; less

than

0.7 mg%, greater than 1.6 mg%, and a group with plasma

levels at

intermediate range. Persons with the lowest ascorbate

intake status had

11-fold the risk of developing cataracts in the

posterior region of the

lens as individuals with the highest ascorbate levels.

 

 

(Table 5 in the original paper contains Dietary

Vitamin E Levels)

 

Reference #29/ Cardiovascular Disease

One of the major signs of peripheral arterial disease

(PAD) is

intermittent claudication. In a double-blind study,

1600 mgs of alpha

tocopherol a day significantly reduced (66%) this

important sign of

cardiovascular disease.

 

#30/Parkinson's Disease

A comparison was made of the clinical picture of

Parkinson's Disease as

measured by a Unified Parkinson's Disease Scale, in

patients taking

vitamin E in dosages from 400 to 3200 IU per day

versus those not

taking

vitamin E. The overall and individual performance,

mentation,

activities

of daily living, motor examination, and complications

of daily living

improved only in the supplemented group.

 

#31/Rheumatoid Arthritis

The use of 1200 mg per day of vitamin E was studied in

rheumatoid

arthritis patients in Austria. The evidence suggests a

strong

relationship between the consumption of vitamin E and

a reduction in

pain and stiffness.

 

#32/ Cataracts

A case control group of 175 cataract patients, 55

years of age or

older,

were matched with a like number of cataract-free

subjects. The

incidence

of cataracts was shown to be half in those consuming

more than 400 IU

of

vitamin E per day.

 

#33/Immune Response

The effect of daily vitamin E supplementation (800 IU

alpha tocopherol

for 30 days) on immune responses of 32 healthy

subjects (60+ years old)

was examined in a placebo-controlled, double-blind

trial in a metabolic

research unit. The data suggest that vitamin E

supplementation improves

immune responsiveness in healthy elderly.

 

(Table 6 in the original paper contains Blood Vitamin

E Levels)

 

Reference #36/ Immune Response

In a metabolic unit, using a double blind protocol,

immune response was

studied in a group receiving vitamin E (8OOmg per day)

versus placebo.

The increased immunocompetence was matched by blood

vitamin E levels

which jumped from 1.1 to 3.1 mg%. No such change in

blood vitamin E

occurred in the control group (1.1 to 1.0 mg%).

 

#14/Alzheimer's Disease

A comparison of vitamin E blood levels in Alzheimer's

Disease (0.8

mg%),

infarct-dementia (0.7 mg%) and in a group of controls

(1.3 mg%)

indicates that the vitamin F levels in the healthy

subjects are

approximately double that in the sick people.

 

#37/ Cataracts

In the Baltimore Longitudinal Study on Aging; using a

case control

design, the prediction of cataracts correlated with

serum vitamin E.

Specifically, those with the lowest blood levels (0.8

mg%) had an odds

ratio of almost double those in the upper terciles

(1.3 mg%).

 

#38/ Macular Degeneration

In the Baltimore Longitudinal Study, it was shown that

those with

macular degeneration (MD) have alpha tocopherol levels

of 0.8 versus

1.3

mg% in the quartile free of MD. Hence, macular

degeneration occurs

twice

as often in patients with low levels.

 

#39/Diabetes

Blood levels following supplementation of 2000 IU of

vitamin F daily

for

two weeks was studied. The average serum tocopherol

increased from 1.48

to 5.06 mg/g. This is the first time levels over 5

mg/g in the blood

have been reported.

 

(Table 7 in the original paper contains Dietary Beta

Carotene Levels)

 

Reference #40/ Cardiovascular Disease

In the Nurses' Health Study in which a cohort of

121,000 US female

nurses ages 30-55 were followed, those who consumed

more than 15-20

mg/day of beta carotene had 40% lower risk of stroke

and 22% lower risk

of heart attack, compared to women who reported eating

less than 6

mg/day.

 

#41/ Cancer

At the moment, this is the largest study of dietary

factors and lung

cancer in nonsmokers. The evidence suggests that

dietary beta carotene

and raw fruits and vegetables reduce the risk of lung

cancer in

nonsmoking men and women.

 

#42/ Immune Response

Immune system response to short-term, high-dose beta

carotene

supplementation was examined. Supplements of 180 mg of

beta carotene

per

day for two weeks increased the number of T4

lymphocytes (helper cells)

and did not effect the T8 lymphocytes (suppressor

cells).

 

#43/ Precancer

In a study of 24 people with oral leukoplakia, given

30 mg/day of beta

carotene for 3 to 6 months, there was a 71% response

rate. Of

particular

importance was the fact that no clinically significant

toxicity was

observed during this trial that could be attributable

to beta carotene.

 

#44/Mortality

A study was conducted regarding the association

between consumption of

vegetables high in beta carotene and cardiovascular

mortality in a

prospective cohort of 1299 elderly Massachusetts

residents.

 

Those consuming the greatest amount (in the upper

quartile) of beta

carotene rich foods had one half the risk of

cardiovascular mortality

as

those in the lowest quartile.

 

(Table 8 in the original paper contains Blood

Carotenoid Levels)

 

Reference #14/ Alzheimer's Disease

The blood carotene levels were 7 to 23 mcg% in

Alzheimer's Disease; 7

to

16 mcg% in multi-infarct dementia patients versus 7 to

82 mcg% in

controls.

 

#45/ Precancer

In oral and pharyngeal cancer, the blood carotene

levels were 39.5 in

cases versus 61.5 mcg% in control patients.

 

#46/Measles

Beta carotene levels were 35.0 mcg% in children with

measles and

kerotomalacia versus 39.0 mcg% in kids with measles

without

kerotomalacia as compared with 64.0 mcg % in health

controls.

 

#47/ Macular Degeneration

The Eye Disease Case Control Study Group discovered

that the chances of

having macular degeneration is reduced about half in

those

demonstrating

the larger amounts of carotenoids in the blood

(greater than 69 mcg%).

 

#48/ Cardiovascular Disease

A 12-year follow-up of cardiovascular mortality in the

Basel

Prospective

Study revealed a significantly increased relative risk

of ischemic

heart

disease and stroke of a magnitude of two-fold at

initially low plasma

levels of carotene (less than 12 mcg%) independent of

the classical

cardiovascular risk factors.

 

 

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Andrew Saul, PhD

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