The Optimum Level of Antioxidants

The epidemiological evidence and the guidelines of the National Cancer Institute and the National Research Council/National Academy of Sciences suggest that at least two fruits and three vegetables per day is a desirable intake.

Since ascorbate, tocopherol, and ß-carotene supplements are inexpensive and high doses are remarkably non-toxic, there is a school that believes that supplements, in addition to a diet containing recommended levels of fruits and vegetables, are desirable.

There is suggestive, but inadequate epidemiological and biochemical evidence bearing on the question. What is clear is that fruits and vegetables contain many necessary micronutrients in addition to antioxidants, some of which also can prevent mutations. Folic acid, for example, is required for the synthesis of the nucleotides in DNA.

Inadequate intake has been shown to cause chromosome breaks and increased cancer and birth defects. Folate deficiency may be a risk factor for myocardial infarction as well. Niacin is required for making poly (ADP-ribose), a component of DNA repair. Other micronutrients are also likely to be part of our defense systems.

The U.S. Recommended Daily Allowances (RDAs) for ascorbate and tocopherol intake--there is no guideline for [[beta]]-carotene independent of its provitamin A activity--are not adequate for several reasons:

1) The amount recommended, e.g., 60 mg/day for ascorbate, is primarily for avoiding an observable deficiency syndrome, e.g., scurvy, and is not necessarily the amount for optimum lifetime health, which is usually not known.

2) A recommended blood level of each antioxidant, e.g., 60 uM ascorbate, would be a more desirable standard. People vary considerably in the intake required to keep their blood level adequate. A smoker, for example, needs to take in several times as much ascorbate as a non-smoker to keep the blood level the same.

Infections may also cause an oxidative stress that leads to antioxidant depletion by activating phagocytic cells. The observation that antioxidant inadequacy is associated with oxidative damage to DNA of the germ line as well as somatic cells, emphasizes the urgency of defining adequate blood levels.

Since only 9% of Americans, and fewer in most other countries, are eating five fruits and vegetables per day, there is a great opportunity to improve health by increasing consumption.

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Oxidant stress, Birth defects, and Childhood Cancer

Oxidative lesions in sperm DNA are increased 250% when levels of dietary ascorbate is insufficient to keep seminal fluid ascorbate to an adequate level. A sizable percentage of the U.S. population ingest inadequate levels of dietary ascorbate, particularly single males, the poor, and smokers. The oxidants in cigarette smoke deplete the antioxidants in plasma. Smokers must eat two to three times more ascorbate than non-smokers to achieve the same level of ascorbate in blood, but they rarely do.

In a comparison of sperm from smokers and nonsmokers Viczian found that the number of sperm and the percent of mobile sperm decrease significantly in smokers, and this decrease is dependent on the dose and duration of smoking.

Paternal smoking, in particular, appears to increase the risk of birth defects and childhood cancer in their offspring. One expects, and finds, a much larger contribution to the germ line mutation rate from the father than the mother, age of the father being an important risk factor. Thus, inadequate diets (and smoking) of fathers appear to result not only in damage to their own DNA but to the DNA of their sperm, an effect that may reverberate down future generations.

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Antioxidants and Cataracts

Cataract removal is the most common operation in the U.S. (1.2 million per year) with costs of over 3 billion dollars.

Taylor has recently reviewed the impressive evidence that cataracts have an oxidative etiology and that dietary antioxidants can prevent their formation in humans. Five epidemiological studies that have examined the effect of dietary antioxidants on cataracts show strong preventative effects of ascorbate, tocopherol, and carotenoids. Those individuals taking daily supplements of ascorbate or tocopherol had about one-third the risk.

Smoking, a severe oxidative stress, is a major risk factor for cataracts and radiation, an oxidative mutagen, is well-known to cause cataracts.

Eye proteins show an increased level of methionine sulfoxide with age and proteins in human cataracts have over 60 percent of their methionine residues oxidized. Pregnant mice depleted of Glutathione, the main sulfhydryl antioxidants in cells, produce offspring with cataracts. The most promising preventative strategy against cataracts appears to be to increase dietary antioxidants and to decrease smoking.

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Tobacco, cancer, and heart disease

Smoking, which we and others argue is a major oxidative stress in addition to a source of mutagens, contributes to about one-third of U.S. cancer, about one-quarter of U.S. heart disease and, about 400,000 premature deaths per year in the U.S..

Tobacco is a major global cause of cancer, but it causes even more deaths by other diseases. Tobacco will cause about 3 million deaths per year worldwide in the l990s and will, at present rates of smoking, cause about l0 million deaths per year a few decades from now.

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Sources and Effects of Oxidants

Four endogenous sources appear to account for most of the oxidants produced by cells:

1) As a consequence of normal aerobic respiration, mitochondria consume molecular oxygen, reducing it by sequential steps to produce H20. Inevitable by-products of this process, as stated above, are O2.-, H202, and .OH. About l012 oxygen molecules are processed by each rat cell daily, and the leakage of partially reduced oxygen molecules is about 2%, yielding about 2x1010 superoxide and hydrogen peroxide molecules per cell per day.

2) Phagocytic cells destroy bacteria or virus-infected cells with an oxidative burst of NO, O2.-, H2O2, and [[macron]]OCl. Chronic infection by viruses, bacteria, or parasites, results in a chronic phagocytic activity and consequent chronic inflammation, which is a major risk factor for cancer. Chronic infections are particularly prevalent in third world countries.

3) Peroxisomes, which are organelles responsible for degrading fatty acids and other molecules, produce H202 as a byproduct, which is then degraded by catalase. Evidence suggests that, under certain conditions, some of the peroxide escapes degradation, resulting in its release into other compartments of the cell and in increased oxidative DNA damage.

4) Cytochrome P450 enzymes in animals constitute one of the primary defense systems against natural toxic chemicals from plants, the major source of dietary toxins. The induction of these enzymes, prevent acute toxic effects from foreign chemicals, but also results in oxidant by-products that damage DNA (Park, J.-Y. K. and Ames, B.N., unpublished).

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Three exogenous sources may significantly increase the large endogenous oxidant load.

1) The oxides of nitrogen (NOx) in cigarette smoke (about 1000 ppm) cause oxidation of macromolecules, and deplete antioxidant levels. This is likely to contribute significantly to the pathology of smoking. Smoking is a risk factor for heart disease as well as a wide variety of cancers in addition to lung cancer.

2) Iron (and copper) salts promote the generation of oxidizing radicals from peroxides (Fenton chemistry). Men who absorb significantly more than normal amounts of dietary iron due to a genetic defect (hemochromatosis disease) are at an increased risk for both cancer and heart disease. It has therefore been argued that too much dietary copper or iron, particularly heme iron (which is high in meat), is a risk factor for cardiovascular disease and cancer in normal men

3) Normal diets contain plant food with large amounts of natural phenolic compounds, such as chlorogenic and caffeic acid, that may generate oxidants by redox cycling .

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Chronic Alcoholism Alters Systemic and Pulmonary Glutathione Redox Status

Rationale: Previous studies have linked the development and severity of acute respiratory distress syndrome with a history of alcohol abuse. In clinical studies, this association has been centered on depletion of pulmonary Glutathione and subsequent chronic oxidant stress.

Objectives: The impact on redox potential of the plasma or pulmonary pools, however, has never been reported.

Methods: Plasma and bronchoalveolar lavage fluid were collected from otherwise healthy alcohol-dependent subjects and control subjects matched by age, sex, and smoking history.

Measurements and Main Results: Redox potential was calculated from measured reduced and oxidized Glutathione in plasma and lavage. Among subjects who did and did not smoke, lavage fluid Glutathione redox potential was more oxidized in alcohol abusers by approximately 40 mV, which was not altered by dilution. This oxidation of the airway lining fluid associated with chronic alcohol abuse was independent of smoking history. A shift by 20 mV in plasma Glutathione redox potential, however, was noted only in subjects who both abused alcohol and smoked.

Conclusions: Chronic alcoholism was associated with alveolar oxidation and, with smoking, systemic oxidation. However, systemic oxidation did not accurately reflect the dramatic alcohol-induced oxidant stress in the alveolar space.

Although there was compensation for the oxidant stress caused by smoking in control groups, the capacity to maintain a reduced environment in the alveolar space was overwhelmed in those who abused alcohol. The significant alcohol-induced chronic oxidant stress in the alveolar space and the subsequent ramifications may be an important modulator of the increased incidence and severity of acute respiratory distress syndrome in this vulnerable population.
Mary Y. Yeh1, Ellen L. Burnham2, Marc Moss2 and Lou Ann S. Brown1

Another Great Reason to Quit Smoking

Cigarettes also contribute to glutathione deficiency because they speed up the rate of glutathione usage in the body. If you have Chronic Fatigue Syndrome, you should quit smoking. If you don’t have Chronic Fatigue Syndrome, you should quit smoking.

Notes: Always consult with your health practitioner before you start or stop any routine that may affect your Chronic Fatigue Syndrome. For management of your symptoms, try Max GXL . This safe and natural supplement has been proven effective against Chronic Fatigue.

Glutathione's three major roles in the body are summarized by the letters A-B-C.
- Anti-oxidant
- Blood Booster
- Cell Detoxifier