***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Dietary epidemiology has been highly successful in identifying the responsible agent in many diseases , including scurvy , pellagra , blindness , and spinal bifida . Case-control , cohort , and ecologic observational studies have consistently associated increased consumption of fruits and vegetables with a decreased risk for a wide variety of epithelial cancers and , in many cases , specific dietary components seem to decrease the risk for a wide array of epithelial cancers . Over time , there has been enthusiasm for one or another compounds , such as β-carotene in the past and folate currently . Despite the success of translating similar epidemiologic observations to clinical benefit in other areas of medicine via the crucible of the r and omized clinical trial , this strategy has not been nearly as successful for cancer . We propose that the inability of nutritional epidemiology to identify effective chemopreventive strategies is not just a problem of quantitation , but rather that the discipline is usually qualitatively incapable of identifying a dietary compound(s ) that will be efficacious . One needs to consider the following basic questions in trying to underst and why nutritional epidemiology has not been translated into progress in cancer prevention : Why do fruits and vegetable show a consistent protective effect against many epithelial cancers in epidemiologic studies ? Once a specific dietary compound is identified as protective in observational studies , why do most subsequent observational studies confirm the effect ? Why are dietary epidemiology observations frequently not confirmed by the r and omized clinical trial ? We call the identified problems “ fishing with only one bait ” and the “ four-legged stool problem . ” The considerations identified in this analysis offer a number of possible solutions to puzzling findings : ( a ) Fruits and vegetables consistently show a protective effect against cancer in observational studies because they represent the entire “ biological action package . ” ( b ) Dietary compounds show a protective effect in observational studies , but not in clinical trials , because this is an inevitable consequence of one compound being falsely identified as the active agent in a system in which multiple agents or multiple interacting regulatory molecules underlie the biological effect . The consequences are serious for trying to use epidemiology to identify effective nutritional compounds . The major conclusion has to be as follows : Supplementation with single dietary compounds is rarely going to be as effective as epidemiologic studies suggest ; it is the biological action package that determines efficacy . Options for how we should move forward will be discussed . Dietary observational epidemiology is complex and involves many biases and confounders . We need to be more critical in the design of large r and omized trials based on observational epidemiology or analysis . Rules of evidence are frequently ignored or misunderstood although the limitations of observational epidemiology are analogous to the problems associated with discovery-based research and biomarker identification . We need to be much more self-critical in the important and critical assessment of dietary compounds and their role in cancer prevention given the very high appeal for this approach both within the lay and scientific communities Controlled trials that use r and omized allocation are the best tool to control for bias and confounding in trials testing clinical interventions . Investigators must be sure to include information that is required by the reader to judge the validity and implication s of the findings in the reports of these trials . In part , complete reporting of trials will allow clinicians to modify their clinical practice to reflect current evidence toward the improvement of clinical outcomes . The consoli date d st and ards of reporting trials ( CONSORT ) statement was developed to assist investigators , authors , review ers , and editors on the necessary information to be included in reports of controlled clinical trials . The CONSORT statement is applicable to any intervention , including herbal medicinal products . Controlled trials of herbal interventions do not adequately report the information suggested in CONSORT . Recently , reporting recommendations were developed in which several CONSORT items were elaborated to become relevant and complete for r and omized controlled trials of herbal medicines . We expect that these recommendations will lead to more complete and accurate reporting of herbal trials . We wrote this explanatory document to outline the rationale for each recommendation and to assist authors in using them by providing the CONSORT items and the associated elaboration , together with examples of good reporting and empirical evidence , where available , for each . These recommendations for the reporting of herbal medicinal products presented here are open to revision as more evidence accumulates and critical comments are collected BACKGROUND Evidence has accumulated from observational studies that people eating more fruits and vegetables , which are rich in beta-carotene ( a violet to yellow plant pigment that acts as an antioxidant and can be converted to vitamin A by enzymes in the intestinal wall and liver ) and retinol ( an alcohol chemical form of vitamin A ) , and people having higher serum beta-carotene concentrations had lower rates of lung cancer . The Beta-Carotene and Retinol Efficacy Trial ( CARET ) tested the combination of 30 mg beta-carotene and 25,000 IU retinyl palmitate ( vitamin A ) taken daily against placebo in 18314 men and women at high risk of developing lung cancer . The CARET intervention was stopped 21 months early because of clear evidence of no benefit and substantial evidence of possible harm ; there were 28 % more lung cancers and 17 % more deaths in the active intervention group ( active = the daily combination of 30 mg beta-carotene and 25,000 IU retinyl palmitate ) . Promptly after the January 18 , 1996 , announcement that the CARET active intervention had been stopped , we published preliminary findings from CARET regarding cancer , heart disease , and total mortality . PURPOSE We present for the first time results based on the pre-specified analytic method , details about risk factors for lung cancer , and analyses of subgroups and of factors that possibly influence response to the intervention . METHODS CARET was a r and omized , double-blinded , placebo-controlled chemoprevention trial , initiated with a pilot phase and then exp and ed 10-fold at six study centers . Cigarette smoking history and status and alcohol intake were assessed through participant self-report . Serum was collected from the participants at base line and periodically after r and omization and was analyzed for beta-carotene concentration . An Endpoints Review Committee evaluated endpoint reports , including pathologic review of tissue specimens . The primary analysis is a stratified logrank test for intervention arm differences in lung cancer incidence , with weighting linearly to hypothesized full effect at 24 months after r and omization . Relative risks ( RRs ) were estimated by use of Cox regression models ; tests were performed for quantitative and qualitative interactions between the intervention and smoking status or alcohol intake . O'Brien-Fleming boundaries were used for stopping criteria at interim analyses . Statistical significance was set at the .05 alpha value , and all P values were derived from two-sided statistical tests . RESULTS According to CARET 's pre-specified analysis , there was an RR of 1.36 ( 95 % confidence interval [ CI ] = 1.07 - 1.73 ; P = .01 ) for weighted lung cancer incidence for the active intervention group compared with the placebo group , and RR = 1.59 ( 95 % CI = 1.13 - 2.23 ; P = .01 ) for weighted lung cancer mortality . All subgroups , except former smokers , had a point estimate of RR of 1.10 or greater for lung cancer . There are suggestions of associations of the excess lung cancer incidence with the highest quartile of alcohol intake ( RR = 1.99 ; 95 % CI = 1.28 - 3.09 ; test for heterogeneity of RR among quartiles of alcohol intake has P = .01 , unadjusted for multiple comparisons ) and with large-cell histology ( RR = 1.89 ; 95 % CI = 1.09 - 3.26 ; test for heterogeneity among histologic categories has P = .35 ) , but not with base-line serum beta-carotene concentrations . CONCLUSIONS CARET participants receiving the combination of beta-carotene and vitamin A had no chemopreventive benefit and had excess lung cancer incidence and mortality . The results are highly consistent with those found for beta-carotene in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study in 29133 male smokers in Finl and We determined whether serum carotenoid or retinol concentrations were altered by beta-carotene supplementation in the Alpha-Tocopherol , Beta-Carotene Cancer Prevention Study and whether such effects were modified by alcohol consumption or cigarette use . Participants in this sub study were 491 r and omly selected men aged 58 - 76 y from the metropolitan Helsinki study center [ 237 receiving supplemental beta-carotene ( 20 mg/d ) and 254 not receiving such supplementation ] .  Dietary carotenoids , retinol , and alcohol , and serum beta-carotene , alpha-tocopherol , retinol , and cholesterol were assessed at baseline . After an average of 6.7 y of supplementation , serum was collected and carotenoid ,  retinol , and alpha-tocopherol concentrations were determined by HPLC . Serum carotenoid fractions were highly correlated with each other ( P < or = 0.0001 ) . Compared with the unsupplemented group , the beta-carotene group had significantly higher serum concentrations of beta-carotene ( 1483 % ) , alpha-carotene ( 145 % ) , and beta-cryptoxanthin ( 67 % ) ( P < or = 0.0001 ) . Retinol concentrations were 6 % higher ( P = 0.03 ) and lutein was 11 % lower ( P = 0.02 ) in the supplemented group . Serum lycopene , zeaxanthin , and alpha-tocopherol did not differ according to beta-carotene-supplementation status . Although these beta-carotene-group differences were not significantly altered by amount of alcohol consumption , higher consumption ( > 12.9 g/d , median ) was related to lower ( 10 - 38 % ) concentrations of carotenoids , particularly beta-carotene , alpha-carotene , and beta-cryptoxanthin , in both the supplemented and unsupplemented groups . Smoking status did not significantly influence the supplementation-related differences in serum carotenoid and retinol values but concentrations of carotenoids were generally highest in participants who quit smoking while in the study and lowest in current smokers of > or = 20 cigarettes/d . This study showed that serum concentrations of non-beta-carotene carotenoids are altered by long-term beta-carotene supplementation and confirms the adverse effects of alcohol and cigarette smoking on serum carotenoids BACKGROUND The Beta-Carotene and Retinol Efficacy Trial ( CARET ) tested the effect of daily beta-carotene ( 30 mg ) and retinyl palmitate ( 25,000 IU ) on the incidence of lung cancer , other cancers , and death in 18,314 participants who were at high risk for lung cancer because of a history of smoking or asbestos exposure . CARET was stopped ahead of schedule in January 1996 because participants who were r and omly assigned to receive the active intervention were found to have a 28 % increase in incidence of lung cancer , a 17 % increase in incidence of death and a higher rate of cardiovascular disease mortality compared with participants in the placebo group . METHODS After the intervention ended , CARET participants returned the study vitamins to their study center and provided a final blood sample . They continue to be followed annually by telephone and mail self-report .  Self-reported cancer endpoints were confirmed by review of pathology reports , and death endpoints were confirmed by review of death certificates . All statistical tests were two-sided . RESULTS With follow-up through December 31 , 2001 , the post-intervention relative risks of lung cancer and all-cause mortality for the active intervention group compared with the placebo group were 1.12 ( 95 % confidence interval [ CI ] = 0.97 to 1.31 ) and 1.08 ( 95 % CI = 0.99 to 1.17 ) , respectively . Smoothed relative risk curves for lung cancer incidence and all-cause mortality indicated that relative risks remained above 1.0 throughout the post-intervention follow-up . By contrast , the relative risk of cardiovascular disease mortality decreased rapidly to 1.0 after the intervention was stopped . During the post-intervention phase , females had larger relative risks of lung cancer mortality ( 1.33 versus 1.14 ; P = .36 ) , cardiovascular disease mortality ( 1.44 versus 0.93 ; P = .03 ) , and all-cause mortality ( 1.37 versus 0.98 ; P = .001 ) than males . CONCLUSIONS The previously reported adverse effects of beta-carotene and retinyl palmitate on lung cancer incidence and all-cause mortality in cigarette smokers and individuals with occupational exposure to asbestos persisted after drug administration was stopped although they are no longer statistically significant . Planned subgroup analyses suggest that the excess risks of lung cancer were restricted primarily to females , and cardiovascular disease mortality primarily to females and to former smokers BACKGROUND In observational studies , individuals with high intakes of fruits and vegetables containing beta-carotene experience lower risks of developing cancer . However , the few r and omized trials of beta-carotene supplementation show no overall benefits ; some even suggest harm . This trial was design ed to test the effects of  beta-carotene supplementation in women . METHODS The Women 's Health Study is a r and omized , double-blind , placebo-controlled trial originally testing aspirin , vitamin E , and beta-carotene in the prevention 
    Output:
    
Although some studies demonstrated benefits , there was insufficient evidence overall to support the use of vitamin A or related retinoids for the treatment or prevention of lung cancers .
Retinyl palmitate combined with beta carotene increased risk of lung cancer in smokers in the large CARET trial .
There is a lack of evidence to support the use of naturally occurring retinoids for the treatment and prevention of lung cancers .