Oxygen Free
Radicals and Aging: Part III
In preceding
articles (part I and
part II of this series), we outlined the relationship between
oxidative damage, aging, and chronic degenerative diseases. We reviewed
various epidemiological and experimental studies which showed that oxidative
damage is not only involved in the development of many age-associated
degenerative diseases, but may be a prime cause of aging itself. These studies
thus provide a strong rationale for using antioxidant supplements to prevent
or treat age-related diseases caused by oxidative damage.
In this article,
we are going to review some convincing evidence that antioxidant supplements
like carotenoids, flavonoids, Ginkgo Biloba, N-acetyl cysteine (NAC) and
vitamins C and E, are effective in alleviating degenerative diseases — as
well as delaying the ravages of aging.1-6 Antioxidants offer tremendous
benefits to individuals suffering from different chronic diseases. They also
protect those who are at risk who want to prevent the development of these
diseases. I will also recommend specific antioxidant supplements and their
dosages for the prevention and supplemental treatment of the following
diseases:
Cancer
Because cancer is
the second leading cause of death in most developed countries,7 cancer therapy
with antioxidants has been extensively researched. Investigators have examined
the benefits of various antioxidants in individuals with different types of
cancers, or who were at risk for developing them. They found that antioxidants
appear to be organ/tissue specific with regard to their effectiveness in both
the prevention and treatment of cancer. Consequently, I will discuss the use
of various antioxidant protocols for prevention and supplemental treatment
with regard to the different types of cancer.
Lung Cancer
Lung cancer develops as a result of chronic injury to the epithelium by
oxidants and other carcinogens. NAC, which possesses both antimutagenic and
anticarcinogenic properties, has emerged as a major preventive agent for lung
cancer8 as well as most other diseases of the lung, including asthma,
emphysema, and pulmonary fibrosis. NAC itself is an antioxidant, and acts to
profoundly increase the production of glutathione, a major cellular
antioxidant. Also, flavonoid intake is associated with low risk for lung
cancer.9 Flavonoid supplements include Quercetin, Hesperidin, Bilberry extract
and Soy extract.
Colorectal
Cancer
Colorectal cancer is the second most common cause of cancer deaths for both
males and females in the U.S.! Oxidative damage plays a significant role in
the development of this cancer. These oxidants are produced as a result of
normal digestive metabolism. The slower the "transit time" of stool in the
colon, the greater the concentration of these cancer-causing free radicals.
Consequently, tissue damage increases as bowel habits become less regular, and
the cancer-susceptible mucous membranes of the colon are exposed to the
progressively more active cancer-causing oxidative agents for longer periods
of time.
This is
illustrated by the increased incidence of cancer as digestive products
progress through the colon toward the rectum (Figure 1). Thus, it appears that
the best way to prevent colon cancer is to maintain a rapid colonic transit
time (in other words, follow Mom's advice and have a bowel movement each
day). This recommendation was also made by Dr. David Reuben in his book, The
Save Your Life Diet. Dr. Reuben also recommended that stools should be ten
inches long, and that they should float! To insure this rapid transit time
(less than 24 hours), he recommended drinking plenty of water, and eating lots
of fiber. The amount of fiber should be whatever it takes to meet the three
criteria above (i.e., daily, 10" length, and buoyant!).
Chitosan and other
forms of soluble and insoluble fibers, like apple pectin, guar gum, and oat
bran fiber, are effective in both speeding transit time and reducing the
incidence of colon cancer. Antioxidants that are effective in chemoprevention
of colorectal cancer include NAC, and vitamins A, C and E.10
Breast Cancer
In a very exciting recent study, investigators examined the effect of
antioxidants in high risk patients with breast cancer.11 32 patients (aged
32-81 years) were considered "high risk" because the tumor had already
spread to the lymph nodes in the armpit. The patients were given a combination
of vitamins C (2,850 mg) and E (2,500 IU), beta carotene (32.5 IU), selenium
(387 mg) and coenzyme Q10 (90 mg), plus other secondary vitamins and minerals
each day, and were monitored for 18 months. Amazingly, none of the patients
died during the study period! Without supplementation, at least four patients
would have been expected to have died. In addition, none of the patients
showed any signs of further cancer spread (metastasis), and the quality of
life was dramatically improved, as exemplified by reduction of pain medication
and gain in weight. Six patients even showed apparent partial remission.
In a subsequent
paper by these same authors, they reported that in one of the six patients who
experienced a remission, her dosage of CoQ10 was increased to 390 mg per day.
In one month, the tumor could no longer be felt, and in another month, the
tumor could not be seen on a mammogram! Encouraged, the physicians treated
another patient (not in the original study) who had a verified breast cancer,
with 300 mg of CoQ10 per day. After 3 months, the patient felt well, and,
again, the tumor could not be found. One of the authors remarked that he had
treated about 200 breast cancer patients per year for 35 years, and he had
never seen a spontaneous complete regression of a 1.5-2.0 cm breast tumor (as
did the patient), and had never seen a comparable regression on any
conventional anti-tumor therapy. (Since reading this article several years
ago, I have placed all of my cancer patients on 300 mg CoQ10 per day — WD).
Cervical Cancer
Oxidative damage has been implicated as a cause of cervical cancer — one of
the most common causes of death of women. Deficiencies in beta carotene, and
vitamins A, C, and E have been identified as being risk factors for developing
cervical cancer. Consequently, an abundance of these supplements certainly
seems to be a rational preventive and potentially therapeutic approach for
anyone at risk of developing — or suffering from — this type of cancer.12
Head and Neck
Cancers
Radiation is a known source of exogenous free radicals, and radiation therapy
is associated with the development of secondary tumors in head and neck cancer
patients. Anyone undergoing radiation therapy would certainly derive
protection with antioxidants like beta carotene and vitamin E.13
Skin Cancer
Sunburn is one of the major causes of skin cancer — especially malignant
melanoma. Whereas there is still argument about the effect of sunscreens for
prevention, compounds with antioxidant activity such as green tea and red wine
extracts (polyphenols) offer a great deal of protection against skin
cancers.14 Other antioxidants that provide protection against skin cancer
include vitamins C and E, glutathione, PABA, NAC and selenium.
Stomach Cancer
Recently, it has been found that free radical damage plays an important role
in the development of gastroduodenal disease, in combination with other risk
factors, including the bacterium H. pylori. The use of high doses of beta
carotene, and vitamins C and E cause a profound decrease in the risk of
development of stomach cancer.15
Cardiovascular
Disease
There is strong
evidence from epidemiological and experimental studies that implicate
oxidative damage in the etiology of heart disease, and which also supports the
use of antioxidants in its prevention. It is now well established that high
doses of vitamin E are very effective in preventing heart disease,16 as are
antioxidants like lipoic acid, CoQ10 and taurine. Other supplements that have
been reported to help in reducing the risk of death from heart disease in
elderly people include green tea and red wine extracts.17 NAC is also a
valuable therapeutic agent in preventing and reducing coronary artery damage
caused by angioplasty.18
Diseases Of
The Central Nervous System
In part II of this series, I
pointed out that the brain and the nervous system are highly prone to
oxidative damage because of their high contents of polyunsaturated fatty acids
and low content of antioxidant enzymes. Furthermore, several areas of the
human brain contain high concentrations of iron which is known to promote free
radical production. Based on these facts, there is a growing interest in the
use of antioxidants for both treatment and prevention of deterioration in
cognitive function associated with aging. Another approach is the use of
chelating agents like chlorella and EDTA to remove the free radical-promoting
heavy metals like iron, mercury and aluminum.
Alzheimer's
Disease
Ginkgo Biloba, beta carotene and vitamins C and E are very effective in
prevention or treatment of impaired cognitive function in elderly subjects,
including those suffering from Alzheimer's disease.19-21
Parkinson's
Disease
Hydrogen peroxide (H2O2) is an oxidant that has been implicated in the
pathogenesis of Parkinson's disease.22 One possible source of this oxidant
is the monoamine oxidase (MAO) system involved in the turnover of dopamine,
whose deficiency underlies the pathogenesis of Parkinson's disease.22 Since
oral glutathione supplementation may not be efficient in sufficiently raising
glutathione levels in tissues, NAC would be an ideal supplement in the battle
against the devastating effects of Parkinson's disease. It has also been
suggested that other antioxidants, including vitamins C and E, may be helpful
adjuvant therapies in Parkinson's disease,23 as well as the MAO type B
inhibitor drug, Deprenyl. Deprenyl has recently been found to have potent
antioxidant properties, and has been recognized as a major breakthrough in the
treatment of Parkinson's. Discovery brand Liquid Deprenyl appears to be the
most effective version of this drug. VRP's customer service reps can provide
their phone number and address.
Stroke
Cerebrovascular disease is a leading cause of death in many areas of the
world. It has been reported that certain antioxidant supplements, including
beta carotene, vitamin E, and selenium, can significantly reduce mortality
from this disease.4
Inflammatory
Disease
It has been
suggested that age-associated decreases in cell-mediated immunity may be
caused by antioxidant depletion.24 Antioxidant depletion has therefore been
proposed as a major risk factor in rheumatoid arthritis26 and inflammatory
bowel disease.26 Vitamin E, b-carotene, and selenium have all demonstrated
efficacy in mitigating inflammatory diseases.25
Diabetes
Oxidative damage
has also been implicated in the pathogenesis of both type 1 and type 2
diabetes, as well as the many complications of diabetes. A wide range of
antioxidants can be used to prevent age-associated diabetes and its
complications. (See previous review: Fat, Obesity, Diabetes and Supplements,
Vitamin Research News Vol 10, numbers 6 & 7, 1996).
Macular
Degeneration and Cataracts
Oxidative damage
to the lens of the eye with increase in age is a major cause of cataract
formation.24,27 Specifically, glutathione depletion has been implicated in the
etiology of this eye disorder.27 Therefore, whereas some other antioxidant
supplements may be helpful, NAC, lipoic acid and taurine would be the most
appropriate supplements for the prevention of cataract formation and macular
degeneration.27
Dose-response
Effects of Antioxidants
The most often
asked question by prospective antioxidant users is, "What antioxidant and
what dose should I use?" The choice of antioxidants and their doses depends
on the particular purpose for which supplementation is desired. For disease
prevention, moderate dosages of a combination of antioxidants is generally
recommended, since antioxidants work best when combined.4,6 For adjuvant
therapies in disease, high doses of antioxidants are required for beneficial
effects, as illustrated in the study with ‘high risk' breast cancer
patients who received a daily combination of 2,850 mg vitamin C, 32 IU of
beta-carotene, 387 mg of selenium and 90-300 mg of CoQ10, along with secondary
vitamins and minerals for 18 months.11 Also, as was evident in the same study,
antioxidant supplements are extremely safe, even when used at high doses for
adjuvant therapy in disease.
It is difficult in
one short article to provide exact doses for each of the multitude of
antioxidants available. However, for the most widely used supplements the
effective daily doses that have been reported for disease prevention are:
vitamin E (400 IU-1200 IU); vitamin C (500-10,000 mg); NAC (600-2,000 mg);
beta-carotene (15-30 mg); Ginkgo Biloba (120 mg). I hope this review about the
effectiveness of various antioxidants in different diseases associated with
aging will be useful in determining the appropriate doses of relevant
supplements.
