Antioxidants in Health and Disease: The Big Picture

[Guest guest]

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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39. Bierenbaum, M.L., Noonan, F.J., Machlin, L.J., Machim, S., Stier,

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40. Manson, J.E., Stampfer, M.J., Willett, W.C., et al. A Prospective

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41 Mayne, S.T., Janerish, D.T., Greenwald, P., Shorost, S., Tucci, C.,

Zaman, M.B., Melamed, M.R., Kiely, M., McKneally, M.F. Dietary Beta

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42. Alexander, M., Newmark, H., Miller, R.G. Oral Beta Carotene Can

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43. Garewal, H.S., Meyskens, F.L., Killen, D., Reeves, D., Kiersch,

T.A., Ellerson, H., Strosberg, A., King, D., Steinbronn, K. Response of

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44. Gaziano, M., Manson, J.E., Branch, L.G., LaMotte, F., Colditz, G.A.,

Buring, J.E., Hennekens, C.H. Dietary Beta Carotene and Decreased

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45. Ibrahim, K., Jafarey, N.A., Zuberi, S.J. Plasma Vitamin A and

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46. Laditan, A.A.O., Fafunso, M. Serum Levels of Vitamin A, Beta

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48. Gey, K.F., Stahelin, H.B., Eichholzer, M. Poor Plasma Status of

Carotene and Vitamin C is Associated with Higher Mortality from Ischemic

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49. Roncucci, L., DiDonato, P., Carati, L., Ferreri, A., Perini, M.,

Bertoni, G., Bedogni, G., Paris, B., Syanoni, F., Girola, M., Ponz de

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50. Heliovaara, M., Knekt, P., Aho, K., Aaran, R.K., Aromaa, A. Serum

Antioxidants and Risk of Rheumatoid Arthritis. Annals of the Rheumatic

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51. Eichholzer, M., Stahelin, H.B., Gey, K.F. Inverse Correlation

Between Essential Antioxidants in Plasma and Subsequent Risk to Develop

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Follow-up of the Prospective Basel Study. EXS 62:398-410, 1992.

 

52. Manson, J.E., Stampfer, M.J, Willett, W.C., Colditz, G.A., Speizer,

F.E., Hennekens, C.H. Antioxidant Vitamins and Secondary Prevention of

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1-70, October 1993.

 

 

 

 

 

Andrew Saul, PhD

--

 

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