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Glutathione and Vitamin C Defense Systems

Source: Theodore Hersh, MD, MACG
Professor of Medicine, Emeritus, Emory University 

No Copyright Infringement Intended

Vitamin C accumulates as a free radical unless this ascorbate is reduced by L-glutathione to ascorbic acid. Indeed, various recent studies have documented that high doses of vitamin C are followed by oxidative stress as evidenced by increased levels of markers of lipid peroxidation and damage to DNA.

Podmore and co-workers reported an increased level of a marker of DNA damage in lymphocytes of healthy volunteers taking 500mg vitamin C daily for six weeks. Ascorbate blood levels were also increased. This damage to DNA by vitamin C reflects a potentially mutagenic cellular lesion. (Nature 1998; 392: 559)

Moreover, Nyyssonen found that oral supplementation also of 500 mg vitamin C daily for two months alone without any other antioxidant in smoking men promoted oxidative stress as evidenced by increased levels in markers of lipid peroxidation. (Eur J Clin Nutr 1997; 51: 154-163) Other studies using single dose Beta Carotene, which also accumulates as a free radical revealed an increase in cancer and cardiovascular disease in individuals who are already at high risk, such as smokers (Hennekens, C.H. et al NEJM 1996; 334: 1145-1149)

Experiments in hamster buccal mucosa have shown that vitamin C applied topically enhances the development of carcinomas in the buccal mucosa. (Schwartz, J et al, Oral Surg Med Pathol 1993; 76: 718-722)

In a study on the use of antioxidants to improve photoprotection in human skin, Steenvoorden and Van Henegouwen reported the best results they obtained on avoidance of UV damage were with the use of synergistic antioxidants. They showed too that “too much” of a single component like vitamin C could have deleterious effects accelerating photoaging.

Smokers and Periodontal Disease: The Role of Antioxidant Therapy

Dentists and other professionals involved with the science of oral hygiene have dealt with a number of symptoms and pathologies of the mouth, gum and teeth. Periodontal disease, which includes inflammation of the gums, is one of the most prevalent health problems in the world and is the major cause of tooth loss in the adult population. Compelling evidence indicates that periodontitis is initiated and exacerbated through tobacco consumption, both smoked and chewed, and may be responsible for more than half of the periodontitis cases among adults in the United States.

Tobacco, whether smoked as cigarettes, cigars or pipe or used as smokeless tobacco, causes devastating effects in the oral cavity. Tobacco smoke has two chances to exert its deleterious effects in the mouth – first, when it is inhaled by the smoker, and second, on its exit during exhalation. In addition to the destruction it does to the gums (gingivitis and periodontitis), smokers have more dental calculus than non-smokers and suffer from increased discoloration of the teeth and bad breath. Over 30,000 new cases of cancer of the oral cavity are diagnosed annually. Oral cancer also kills 8,000 patients each year and only half of the cases diagnosed annually have a five year survival. The good news here is that by understanding exactly how periodontal disease and oral cancers develop, we can begin to take measures to prevent and interfere with the destructive path of these diseases. Prior attempts to treat diseases of the gingiva and oral cavity have failed for they have not recognized the role played by toxic molecules known as “free radicals” and the healing and protective benefits of the endogenous antioxidant defense system.

Periodontal disease is caused by inflammation and infection in both the gingiva and the connective tissue that supports the teeth. There is initially an inflammation in the local blood vessel walls, which accounts for the most common sympton of bleeding gums. This is also accompanied by migration of white blood cells to help combat the tissue invasion by pathogenic mouth bacteria. During this inflammatory reaction, most cells liberate histamine and also locally generate countless toxic free radicals, both of which contribute to tissue pathology. Collagen production may also then be interfered with due to local vitamin C deficiency, which contributes to the swelling and redness of gum tissues.

Cigarette smoke is divided into two phases, tar and gas-phase smoke. Cigarette tar contains high concentrations of free radicals, however, the cigarette filter acts as a “trap” for the free radicals in cigarette tar. By comparison, each puff of a cigarette in the gas-phase smoke is said to contain 1015 of toxic free radicals. The filter does not currently protect the smoker (or the secondary smoker) from these free radicals and left unchecked, these billions of free radicals are free to induce inflammatory reactions (resulting in periodontal disease), destroy cell structure and function and damage DNA, all of which are implicated in oro-pharyngeal diseases and malignancies.

Thankfully, the body has a built-in system of defense from these toxic free radicals – antioxidants. Antioxidants scavenge and neutralize free radical species to a less toxic or non-toxic compound. Antioxidants have also been found to inhibit all stages of carcinogenesis. However, when the body’s built-in antioxidant defense system fails to suppress uncontrolled toxic free radicals in the body due to either an overwhelming production of free radicals such as from smoking or a depletion of critical compounds used by the body’s antioxidant defenses, the body goes into a state of “oxidative stress.” Since oxidative stress leads to disease, free radicals are considered to be contributors to over fifty prevalent and chronic diseases, including cardiovascular disease, immune disorders, neurodegenerative diseases, premature aging and a variety of cancers. Indeed, periodontal disease is now considered a risk factor for atherosclerosis through the genesis of oxidative stress on the vascular tree.
The state of oxidative stress is remedied by increasing antioxidants through diet (fruits and vegetables) and by antioxidant supplements. Reduction of the noxious stimulus of free radicals, such as through the elimination of tobacco abuse, likewise will reduce this oxidative stress. While there are numerous antioxidants within the body, however, the latest scientific studies reveal two critical points: (1) all antioxidants are not equal; and (2) combinations of synergistic antioxidants are far superior to singular antioxidants.

While each of the many antioxidants in the body play a role in ridding the body of excess free radicals, it is the antioxidant known as glutathione that acts as “commander in chief.” Glutathione is found in body fluids and in every cell in the body. Working intra and extra-cellularly in its reduced form, glutathione acts as the body’s key antioxidant, detoxificant and protectant. It is the gatekeeper in the respiratory tract and lining of the gut and has multiple functions in disease prevention and in detoxification of chemicals and drugs. The body uses glutathione to preserve the integrity of cell structure from deterioration and to nullify the effect of toxic free radicals that operate at the cellular level and in extra-cellular fluids.

Glutathione levels inside the cells must be maintained in order to have healthy cells and a strong defense system. Cells die without adequate levels of glutathione, suggesting that glutathione may be a key anti-aging factor. However, glutathione does not work alone. To provide maximum beneficial effects against free radicals, glutathione must work SYNERGISTICALLY with other cellular enzymes and antioxidants such as glutathione peroxidase, selenium and vitamins C and E.

It works like this. One antioxidant molecule attacks and neutralizes one free radical molecule, but in the neutralization process, the antioxidant molecule itself becomes oxidized. It then has to undergo a reduction reaction in order to be regenerated as an antioxidant otherwise it remains as an inert molecule, unable to fulfill its antioxidant function. In some cases, the oxidized by-product is itself a toxic free radical and remains so until it is neutralized or regenerated into an antioxidant again.

This is the point where synergy becomes critical. A singular antioxidant cannot regenerate itself. In order to continue to perform its antioxidant function, each oxidized “antioxidant” must be regenerated by a specific SYNERGISTIC antioxidant or by specific cellular enzymes. In the body, glutathione and selenium assume the pivotal role in this process. In other words, although singular antioxidants such as vitamin C or vitamin E are physiologically useful, once they have accomplished their job, attacking a free radical, they themselves are oxidized and become a free radical. However, if they are combined with other specific synergistic antioxidants, particularly glutathione and selenium, they become rejuvenated and then can continuously do their job – just like the cellular defense system. 

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