Large sample size: 18,314 smokers and asbestos workers o Subjects well-matched at baseline o Primary endpoint: incidence of lung cancer o Targeted length of intervention: 5 years Results: o treatment increased risk of lung cancer Relative risk: 1.28 vs 1.00 o Treatment increased risk of mortality Relative risk: 1.18 vs. 1.00 Conclusions: o Trial stopped in 1996 due to: Higher rates of lung cancer, lung cancer mortality, and all-cause mortality in the treatment group (ethical considerations) 51
o The results of the trial are troubling. There was no support for a beneficial effect of beta-carotene or vitamin A, in spite of large advantages inferred from observational data…of dietary intake or serum levels of beta carotene and vitamin A 6 year follow up o Relative risk of treatment group vs, placebo at discontinuation of intervention and a 6 year-post intervention o Adverse effects still noticeable (but not statistically significant) 6 years after discontinuation of supplements Is it one of those random negative trials? o Many other follow up trials were completed on vitamin A and its prevention of cancer One had a 16% increase in lung cancer o Note that all of the people in these studies were heavy smokers smoking at least 20 cigarettes a day for 36 years o Also each of the individuals actually took the supplements as directed o To conclude: beta carotene supplementation increased lung cancer incidence in smokers Beta-Carotene and lung cancer: conclusions CARET study (USA): high-dose of beta-carotene supplementation increased the risk of lung cancer by 28% and the risk of all-cause mortality by 18% in smokers or people exposed to asbestos CARET study: elevated risk of lung cancer and lung cancer mortality was still elevated 6 years after discontinuation of beta-carotene supplements ATBS study (Finland): high-dose of beta-carotene supplementation increased the risk of lung cancer by 18% in smokers Neither study found a statistical difference before 18-36-month supplementation importance of long-term intervention studies Important Considerations – Subject Population Smokers and patients exposed to asbestos o Lung cancer may have been initiated prior to supplementation intake of antioxidants could have increased survival of cancer cells o Chemical interactions between beta-carotene and cigarette smoke could produce toxic, pro-oxidative products? NOTE: dose is very important! o Low dose of anti-oxidants = anti-oxidant o High doses of anti-oxidants = pro-oxidants RECALL: drugs are absorbed, metabolized, distributed and then excreted creating a parabolic curve Important Considerations – Dose 52
If a little is good…more is better, right? Dose o CARET: 30 mg beta carotene and 25,000 IU retinol daily o ATBS: 20 mg beta carotene or 50 mg alpha-tocopherol daily Vitamin A recommendations for adults o RDA: 1.4-1.8 mg daily; UL: 6 mg daily Serum [beta-carotene] o CARET: 2.1 mg/L (treatment) vs. 0.17 mg/L (placebo) o ATBS: 3.0 mg/L (treatment) vs. 0.18 mg/L (placebo) Take note of the dosage of products available on the market: beta-carotene supplements: o Jamieson = 15 mg tablets o GNC = 12 mg tablets o
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- Fall '16
- risk reduction, Natural Health Products, dietary fibre, health claim