Preventing tobacco smoke diseases by network antioxidants
Abstracts
Initial Award Abstract |
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It has been proposed that various chronic diseases, such as cancer or heart disease, are either caused or made worse by "free radicals." This hypothesis is based on many studies which have shown that consuming a diet rich in fruit and vegetables, or taking antioxidant supplements (especially vitamin C or vitamin E) is related to a low incidence of these diseases.
What are "free radicals" and "antioxidants"? Free radicals are highly reactive molecules that can damage protein, DNA, or fats via an oxidative process. Antioxidants protect cells from free radicals because antioxidants react faster with free radicals than do the cell components. Examples of antioxidants are vitamins E and C. We believe that these antioxidants work together and that a combination of antioxidants (vitamin C, vitamin E, and thiols) are more effective than just one antioxidant alone.
HYPOTHESES
· Exposure to firsthand or secondhand cigarette smoke exposes individuals to free radicals (especially long lived radicals) that cause oxidative damage.
· Antioxidants can ameliorate the oxidative effects of cigarette smoke.
· A special combination of antioxidants (including vitamins E and C, and a thiol) will be more effective than vitamin C alone in preventing oxidative damage of cigarette smoke.
SPECIFIC AIMS
To test our hypotheses, we plan:
PHASE 1: To evaluate the oxidative stress status of smokers, passive smokers, and nonsmokers— blood plasma antioxidants and markers of oxidative damage in plasma and urine will be measured. 500 subjects will be recruited from the Buck Center. Recruitment will be stratified by smoking status (smoker, non-smoker, passive smoker) and vitamin supplement use. All subjects will provide a fasting blood sample and a casual urine specimen for measurement of oxidative damage markers and antioxidants. The results of this study will be used to validate methodologies to find the most sensitive markers of oxidative damage in those exposed to cigarette smoke.
PHASE 2: To evaluate whether antioxidants can improve the oxidative stress status of smokers and passive smokers, we plan an intervention trial with antioxidants. From the individuals that participated in phase 1, we will recruit non-supplement users that are smokers (150 subjects) or are passive smokers (150 subjects). They will be randomized into groups (50 subjects per group) to receive placebo, vitamin C, or the network antioxidant cocktail. Fasting blood samples will be obtained 30 days after the start of phase 1 (unsupplemented), and after 30 and after 60 days of consuming either of the supplements or placebo. For each subject completing phase 2, a total of 4 blood samples will be obtained—2 samples during non-supplementation and 1 sample at 30 days and at 60 days supplementation. This phase will test whether a combination of antioxidants is more efficacious than vitamin C alone in preventing the oxidative damage caused by exposure to cigarette smoke.
Future plans include using these defined indicators of cigarette smoke-related oxidative stress in large scale epidemiological studies where subjects will be recruited via the internet. A web site will be used to disseminate the collected results and as an "educational tool" to supplement other methods designed to motivate subjects to quit smoking. |
Final Report |
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Objectives/Specific Aims. It has been proposed that various chronic diseases, such as cancer or heart disease, are either caused by or made worse by “free radicals.” This hypothesis is based on many studies which have shown that consuming a diet rich in fruit and vegetables, or taking antioxidant supplements is related to a low incidence of these diseases. Free radicals are highly reactive molecules that can damage protein, DNA, or fats via an oxidative process. Antioxidants protect cells from free radicals because antioxidants react faster with free radicals than do the cell components. Examples of antioxidants are vitamin E and C and thiols. We believe that these antioxidants work together and that a combination of antioxidants – an antioxidant cocktail containing vitamin C, E, and a thiol - is more effective than just one antioxidant alone. The objective of this research was to test this hypothesis.
Procedures. To evaluate the oxidative stress status of smokers, passive smokers, and nonsmokers, blood plasma antioxidants and markers of oxidative damage in plasma have been measured in this phase (Phase I). Recruitment was stratified by smoking status and vitamin supplement use. Blood has been measured for oxidative damage markers and antioxidants. Smokers and passive smokers who participated in Phase I entered the intervention phase of the study (Phase II). They were randomized into three groups to receive either placebo or vitamin C or the network antioxidant cocktail. Fasting blood samples were obtained before and after consuming either of the supplements or the placebo (two samples during non-supplementation and one sample after 60 days of supplementation. The intervention phase is testing whether a combination of antioxidants is more efficacious than vitamin C alone in preventing the oxidative damage caused by exposure to cigarette smoke. Progress. The subject recruitment, data collection and assays are completed. Study Results. Treatment for two months with vitamin C significantly reduced F2-isoprostanes in smokers; this marker was also reduced in the Cocktail group, but the effect was smaller and not statistically significant. Smoking is associated with significantly lower plasma levels of vitamin C and three carotenoids antioxidants, beta-carotene, cryptoxanthin and lutein. Passive smokers have significantly lower plasma levels of beta-carotene. The statistical analyses of that study have not all been completed and are the subject of a Continuation Grant Proposal submitted to TRDRP in January 2001. Significance. This study has shown that treatment with vitamin C can reduce one of the markers of oxidative damage, F2-Isoprostanes. While a step removed from proving that increased intake of vitamin C would reduce smoking-related diseases, it does indicate that vitamin C reduces one of the probable mechanisms in the causation of smoking-related diseases. It also has shown that exposure to second-hand smoke as little as one cigarette a day indoors, lowers the body’s antioxidant level and therefore lowers the body’s ability to prevent oxidative damage. |
