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.

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