Antioxidants in Health and Disease: The Big Picture

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Antioxidants in Health and Disease: The Big Picture

E. Cheraskin, MD, DMD

(Reprinted with permission of the author and the Journal of Orthomolecular

Medicine 10: #2, 89-96, Second Quarter, 1995.)

 

Abstract

In December 1993, 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 an inverse 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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