human
***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: We analysed self-reported cold data for 95 pairs of identical twins who took part in a double-blind trial of vitamin C tablets .  One member of each twin pair took vitamin C and the other took a well matched placebo each day for 100 days . Vitamin C had no significant effect except for shortening the average duration of cold episodes by 19 % A r and omized controlled trial of the effect of 1 g ascorbic acid per day in the prevention of the common cold was conducted on 688 adult women . There is evidence of a small reduction by  vitamin C  in the mean number of chest colds , but no evidence of any effect on simple colds . The existence of a subgroup of vulnerable women in the community who benefit from vitamin C was considered but further examination of the data gives no support to this conclusion OBJECTIVE To determine the effect of large doses of vitamin C in the treatment of the common cold . STUDY DESIGN Double-blind , r and omised clinical trial with four intervention arms : vitamin C at daily doses of 0.03 g ( " placebo " ) , 1 g , 3 g , or 3 g with additives ( " Bio-C " ) taken at onset of a cold and for the following two days . PARTICIPANTS AND SETTING 400 healthy volunteers were recruited from staff and students of the Australian National University , Canberra , ACT , between May 1998 and November 1999 . The trial continued for 18 months . INTERVENTIONS Participants were instructed to commence medication when they had experienced early symptoms of a cold for four hours , and to record daily their symptoms , severity , doctor visits and use of other medications . MAIN OUTCOME MEASURES Duration of symptoms and cold episodes ; cumulative symptom severity scores after 7 , 14 and 28 days ; doctor visits ; and whether participants guessed which medication they were taking . RESULTS 149 participants returned records for 184 cold episodes . No significant differences were observed in any measure of cold duration or severity between the four medication groups . Although differences were not significant , the placebo group had the shortest duration of nasal , systemic and overall symptoms , and the lowest mean severity score at 14 days , and the second lowest at 7 and 28 days . CONCLUSIONS Doses of vitamin C in excess of 1 g daily taken shortly after onset of a cold did not reduce the duration or severity of cold symptoms in healthy adult volunteers when compared with a vitamin C dose less than the minimum recommended daily intake In a survey of double-bind design , 3 groups of approximately 70 student volunteers took 1 g L-ascorbic acid , 1 g D-isoascorbic acid , or placebo tablets every day for 15 weeks and the incidence and duration of colds were recorded . The group taking D-isoascrobic acid suffered 34 % fewer colds than the other two groups ; the results were also analyzed in relation to the sex and smoking habits of the volunteers . The rationale for investigating D-isoascorbic acid , an isomer of L-ascorbic acid which has limited antiscorbutic activity , is discussed Self-reported cold data have been analyzed for 95 pairs of identical twins aged 14 - 64 who took part in a double-blind trial of vitamin C tablets .  One member of each twin pair took a tablet containing 1 g vitamin C and the other took a well-matched placebo each day for 100 days . In the total sample there was no effect of vitamin C in preventing colds . However , subdivision of the data showed a significant preventive effect of the placebo in the 51 pairs living together and an equal and opposite preventive effect of the vitamin C in the 44 pairs living apart . The placebo effect in the pairs living together may be attributed to the large proportion who wrongly perceived which treatment they were taking . The reduction of colds in the vitamin C group of the pairs living apart was about 20 % . There were significant correlations between cold symptoms reported and the personality trait of neuroticism . No side effects of substantive changes in serum biochemistry could be attributed to the vitamin C dose Abstract A double-blind study to evaluate vitamin C supplements for  respiratory-Infection prophylaxis  was conducted among 641 children at a Navajo boarding school over a 14-week period . Supplements A r and omised controlled study was carried out of the effect on growth of the provision of free milk supplements to schoolchildren aged 7 and 8 . In selecting children for this study , the aim was to identify those whose socioeconomic circumstances might place them at a disadvantage for growth . Five hundred and eighty-one-children were selected from schools where a high proportion of the pupils received free school meals , and from families with four or more children . The subjects were r and omly allocated to receive a third of a pint ( 190 ml ) of free milk daily for six school terms or to a control group . The mean difference in height gain at the end of twenty-one- and -a-half months was 3 % or 2.93 mm ( P less than 0.05 ) in favour of the children provided with free milk . The mean difference in weight gain was 130 g ( P greater than 0.05 ) in their favour . The height and weight gain associated with the provision of free mild was very small in the study population , and it is therefore likely that the benefit to growth of providing free milk for the whole unselected population of schoolchildren of these ages would be even smaller A r and omised controlled trial was carried out to study the effect of 10 g of ascorbic acid taken during the first 2 1/2 days on the symptoms of the common cold . Altogether 1524 volunteers were recruited from a number of working groups in different parts of the country ; 482 developed colds . There was no evidence that upper respiratory or general constitutional symptoms were alleviated by ascorbic acid . Among the men who had any colds at all , significantly fewer on active than on placebo treatment had two or more colds ; however , this effect was not seen in women . Ascorbic acid is of no value in the treatment of the common cold ; its preventive effect , if any , is not such as to justify advising its general use as a prophylactic measure A large scale double-blind trial was conducted to test the cl aim that the intake of one gram of vitamin C per day substantially reduces the frequency and duration of " colds " . It was found that in terms of the average number of colds and days of sickness per subject the vitamin group experienced less illness than the placebo group , but the differences were smaller than have been cl aim ed and were statistically not significant . However , there was a statistically significant difference ( P < 0.05 ) between the two groups in the number of subjects who remained free of illness throughout the study period . Furthermore the subjects receiving the vitamin experienced approximately 30 % fewer total days of disability ( confined to the house or off work ) than those receiving the placebo , and this difference was statistically highly significant ( P < 0.001 ) . The reduction in disability appeared to be due to a lower incidence of constitutional symptoms such as chills and severe malaise , and was seen in all types of acute illness , including those which did not involve the upper respiratory tract In a large double-blind study among Navaho school children , we evaluated the effects of vitamin C in 1- and 2-gram daily doses on acute respiratory illness during a 14-week period . ' We found no evidence of significant prophylaxis , but our findings did suggest a modest therapeutic benefit in that children taking vitamin Chad from 28 % to 34 % fewer days of morbidity caused by respiratory episodes than those taking placebo . Likewise , in classroom surveillance , younger children on vitamin C had 26 % fewer symptom-days of cough and nasal discharge recorded . These observations were consistent with other recent trials using 1 gram daily ( 4 grams during illness ) in Canadian adults L ' and 250 - 500 milligrams daily in Irish schoolchildren.3 The clinical significance of this modest therapeutic result in minor , selflimited illness was , in itself , question able . However , further study was indicated to determine : ( a ) if use of vitamin C could prevent complications of the common cold in children , such as superinfections or otitis media ; ( b ) if certain symptoms or symptom complexes responded specifically to vitamin C therapy ; and ( c ) if indeed , as our data had suggested , l higher blood ascorbic acid levels were correlated with fewer days of illness . A second investigation was design ed to confirm , if possible , and exp and our previous findings . The second trial was conducted in two Navaho boarding schools during January through May 1974 , using doses of 1 gram vitamin C daily versus placebo tablets . This report presents preliminary routine surveillance findings from the second study Between December 1972 and February 1973 , 2349 volunteers participated in a double-blind trial to assess the effect of large doses of vitamin C on the  incidence and severity of winter illness .  In addition , records were kept but no tablets taken during March . Subjects were r and omly allocated to eight treatment regimens : three prophylactic-only ( daily dose 0.25 , 1 or 2 g ) , two therapeutic-only ( 4 or 8 g on the first day of illness ) , one combination ( 1 g daily and 4 g on the first day of illness ) , and two all-placebo . None of the groups receiving vitamin C showed a difference in sickness experience that was statistically significant from that of the placebo groups , but the results obtained were compatible with an effect of small magnitude from both the prophylactic and therapeutic regimens , and an effect of somewhat greater magnitude from the combination regimen . The combination regimen was associated more with a reduction in severity than frequency of illness , although the extra dosage was limited to the first day of illness . In spite of the eightfold range in daily dose , the three prophylactic-only regimens showed no evidence of a dose-related effect , but the 8 g therapeutic dose was associated with less illness than the 4 g therapeutic dose . There was no evidence of side effects from the 1 and 2 g prophylactic doses of vitamin C , and no evidence of a rebound increase in illness during the month following withdrawal of the daily vitamin supplements . On the basis of this and other studies it is suggested that the optimum daily dose of vitamin C is less than 250 mg , except possibly at the time of acute illness , when a larger daily intake may be beneficial Context Clinical studies of vitamin C as a potential anticancer agent have produced inconsistent results despite in vitro evidence that high concentrations kill cancer cells . Contribution Pharmacokinetic studies in healthy persons , using a depletion-repletion design , show that intravenous administration can achieve 70-fold higher blood levels of vitamin C than the highest tolerated oral dose . Caution s Although this study provides better underst and ing of the pharmacokinetic issues involved in research on vitamin C , it provides no evidence that vitamin C has any effect on cancer cells and can not be used to support its clinical use for therapeutic purpose s. The Editors Vitamin C in gram doses is taken orally by many people and administered intravenously by complementary and alternative medicine practitioners to treat patients with advanced cancer ( 1 , 2 ) . After oral intake ,  vitamin C plasma concentrations are tightly controlled at 70 to 85 mol/L for amounts ( as much as 300 mg daily ) that can be obtained from food ( 3 , 4 ) . However , concentrations achieved by higher pharmacologic doses are uncertain . Despite poor rationale , vitamin C in gram doses was proposed as an anticancer agent decades ago ( 5 ) . Unblinded studies with retrospective or nonr and om controls reported clinical benefit from oral and intravenous vitamin C administered to patients with terminal cancer at a dosage of 10 g daily ( 1 , 6 , 7 ) . Placebo-controlled trials in patients with cancer reported no benefit from oral vitamin C at a dosage of 10 g daily ( 8 , 9 ) , and vitamin C treatment was judged ineffective ( 10 ) . However , in vitro evidence showed that vitamin C  killed cancer cells at extracellular concentrations higher than 1000 mol/L ( 11 , 12 ) , and its clinical use by some practitioners continues . We recognized that oral or intravenous routes could produce substantially different vitamin C concentrations ( 13 ) . We report here that intravenous doses can produce plasma concentrations 30- to 70-fold higher than the maximum tolerated oral doses . These data suggest that the role of vitamin C in cancer treatment should be reexamined , and insights from vitamin C pharmacokinetics can guide its clinical use . Methods Pharmacokinetic Studies in Healthy Persons The study was approved by the Institutional Review Board of the National Institute of Diabetes and Digestive and Kidney Diseases , National Institutes of Health . After we obtained written informed consent , 17 healthy volunteers ( 7 men , 10 women ; age , 19 to 27 years ) were studied as in patients by using a depletion-repletion study design ( 3 , 4 ) . Participants were hospitalized for 3 to 6 months and consumed a  vitamin C-deficient  diet containing less than 0.005 g of vitamin C per day . At plasma vitamin C concentrations less than 8 mol/L , persons were depleted without signs of scurvy . Vitamin C , 0.015 g twice daily , was then administered orally until participants achieved a steady state for this dose ( 0.03 g daily ) . Participants received successive oral daily vitamin C doses of 0.03 g , 0.06 g , 0.1 g , 0.2 g , 0.4 g , 1.0 g , and 2.5 g until a steady state was achieved for each dose . Bioavailability sampling was conducted at a steady state for vitamin C doses of 0.015 g , 0.03 g , 0.05 g 
    Output:
    
agent
REVIEW ERS ' CONCLUSIONS The failure of vitamin C supplementation to reduce the incidence of colds in the normal population indicates that routine mega-dose prophylaxis is not rationally justified for community use .
But evidence shows that it could be justified in persons exposed to brief periods of severe physical exercise and /or cold environments .
Also , the consistent and statistically significant small benefits on duration and severity for those using regular vitamin C prophylaxis indicates that vitamin C plays some role in respiratory defence mechanisms .
***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: We analysed self-reported cold data for 95 pairs of identical twins who took part in a double-blind trial of vitamin C tablets .  One member of each twin pair took vitamin C and the other took a well matched placebo each day for 100 days . Vitamin C had no significant effect except for shortening the average duration of cold episodes by 19 % A r and omized controlled trial of the effect of 1 g ascorbic acid per day in the prevention of the common cold was conducted on 688 adult women . There is evidence of a small reduction by  vitamin C  in the mean number of chest colds , but no evidence of any effect on simple colds . The existence of a subgroup of vulnerable women in the community who benefit from vitamin C was considered but further examination of the data gives no support to this conclusion OBJECTIVE To determine the effect of large doses of vitamin C in the treatment of the common cold . STUDY DESIGN Double-blind , r and omised clinical trial with four intervention arms : vitamin C at daily doses of 0.03 g ( " placebo " ) , 1 g , 3 g , or 3 g with additives ( " Bio-C " ) taken at onset of a cold and for the following two days . PARTICIPANTS AND SETTING 400 healthy volunteers were recruited from staff and students of the Australian National University , Canberra , ACT , between May 1998 and November 1999 . The trial continued for 18 months . INTERVENTIONS Participants were instructed to commence medication when they had experienced early symptoms of a cold for four hours , and to record daily their symptoms , severity , doctor visits and use of other medications . MAIN OUTCOME MEASURES Duration of symptoms and cold episodes ; cumulative symptom severity scores after 7 , 14 and 28 days ; doctor visits ; and whether participants guessed which medication they were taking . RESULTS 149 participants returned records for 184 cold episodes . No significant differences were observed in any measure of cold duration or severity between the four medication groups . Although differences were not significant , the placebo group had the shortest duration of nasal , systemic and overall symptoms , and the lowest mean severity score at 14 days , and the second lowest at 7 and 28 days . CONCLUSIONS Doses of vitamin C in excess of 1 g daily taken shortly after onset of a cold did not reduce the duration or severity of cold symptoms in healthy adult volunteers when compared with a vitamin C dose less than the minimum recommended daily intake In a survey of double-bind design , 3 groups of approximately 70 student volunteers took 1 g L-ascorbic acid , 1 g D-isoascorbic acid , or placebo tablets every day for 15 weeks and the incidence and duration of colds were recorded . The group taking D-isoascrobic acid suffered 34 % fewer colds than the other two groups ; the results were also analyzed in relation to the sex and smoking habits of the volunteers . The rationale for investigating D-isoascorbic acid , an isomer of L-ascorbic acid which has limited antiscorbutic activity , is discussed Self-reported cold data have been analyzed for 95 pairs of identical twins aged 14 - 64 who took part in a double-blind trial of vitamin C tablets .  One member of each twin pair took a tablet containing 1 g vitamin C and the other took a well-matched placebo each day for 100 days . In the total sample there was no effect of vitamin C in preventing colds . However , subdivision of the data showed a significant preventive effect of the placebo in the 51 pairs living together and an equal and opposite preventive effect of the vitamin C in the 44 pairs living apart . The placebo effect in the pairs living together may be attributed to the large proportion who wrongly perceived which treatment they were taking . The reduction of colds in the vitamin C group of the pairs living apart was about 20 % . There were significant correlations between cold symptoms reported and the personality trait of neuroticism . No side effects of substantive changes in serum biochemistry could be attributed to the vitamin C dose Abstract A double-blind study to evaluate vitamin C supplements for  respiratory-Infection prophylaxis  was conducted among 641 children at a Navajo boarding school over a 14-week period . Supplements A r and omised controlled study was carried out of the effect on growth of the provision of free milk supplements to schoolchildren aged 7 and 8 . In selecting children for this study , the aim was to identify those whose socioeconomic circumstances might place them at a disadvantage for growth . Five hundred and eighty-one-children were selected from schools where a high proportion of the pupils received free school meals , and from families with four or more children . The subjects were r and omly allocated to receive a third of a pint ( 190 ml ) of free milk daily for six school terms or to a control group . The mean difference in height gain at the end of twenty-one- and -a-half months was 3 % or 2.93 mm ( P less than 0.05 ) in favour of the children provided with free milk . The mean difference in weight gain was 130 g ( P greater than 0.05 ) in their favour . The height and weight gain associated with the provision of free mild was very small in the study population , and it is therefore likely that the benefit to growth of providing free milk for the whole unselected population of schoolchildren of these ages would be even smaller A r and omised controlled trial was carried out to study the effect of 10 g of ascorbic acid taken during the first 2 1/2 days on the symptoms of the common cold . Altogether 1524 volunteers were recruited from a number of working groups in different parts of the country ; 482 developed colds . There was no evidence that upper respiratory or general constitutional symptoms were alleviated by ascorbic acid . Among the men who had any colds at all , significantly fewer on active than on placebo treatment had two or more colds ; however , this effect was not seen in women . Ascorbic acid is of no value in the treatment of the common cold ; its preventive effect , if any , is not such as to justify advising its general use as a prophylactic measure A large scale double-blind trial was conducted to test the cl aim that the intake of one gram of vitamin C per day substantially reduces the frequency and duration of " colds " . It was found that in terms of the average number of colds and days of sickness per subject the vitamin group experienced less illness than the placebo group , but the differences were smaller than have been cl aim ed and were statistically not significant . However , there was a statistically significant difference ( P < 0.05 ) between the two groups in the number of subjects who remained free of illness throughout the study period . Furthermore the subjects receiving the vitamin experienced approximately 30 % fewer total days of disability ( confined to the house or off work ) than those receiving the placebo , and this difference was statistically highly significant ( P < 0.001 ) . The reduction in disability appeared to be due to a lower incidence of constitutional symptoms such as chills and severe malaise , and was seen in all types of acute illness , including those which did not involve the upper respiratory tract In a large double-blind study among Navaho school children , we evaluated the effects of vitamin C in 1- and 2-gram daily doses on acute respiratory illness during a 14-week period . ' We found no evidence of significant prophylaxis , but our findings did suggest a modest therapeutic benefit in that children taking vitamin Chad from 28 % to 34 % fewer days of morbidity caused by respiratory episodes than those taking placebo . Likewise , in classroom surveillance , younger children on vitamin C had 26 % fewer symptom-days of cough and nasal discharge recorded . These observations were consistent with other recent trials using 1 gram daily ( 4 grams during illness ) in Canadian adults L ' and 250 - 500 milligrams daily in Irish schoolchildren.3 The clinical significance of this modest therapeutic result in minor , selflimited illness was , in itself , question able . However , further study was indicated to determine : ( a ) if use of vitamin C could prevent complications of the common cold in children , such as superinfections or otitis media ; ( b ) if certain symptoms or symptom complexes responded specifically to vitamin C therapy ; and ( c ) if indeed , as our data had suggested , l higher blood ascorbic acid levels were correlated with fewer days of illness . A second investigation was design ed to confirm , if possible , and exp and our previous findings . The second trial was conducted in two Navaho boarding schools during January through May 1974 , using doses of 1 gram vitamin C daily versus placebo tablets . This report presents preliminary routine surveillance findings from the second study Between December 1972 and February 1973 , 2349 volunteers participated in a double-blind trial to assess the effect of large doses of vitamin C on the  incidence and severity of winter illness .  In addition , records were kept but no tablets taken during March . Subjects were r and omly allocated to eight treatment regimens : three prophylactic-only ( daily dose 0.25 , 1 or 2 g ) , two therapeutic-only ( 4 or 8 g on the first day of illness ) , one combination ( 1 g daily and 4 g on the first day of illness ) , and two all-placebo . None of the groups receiving vitamin C showed a difference in sickness experience that was statistically significant from that of the placebo groups , but the results obtained were compatible with an effect of small magnitude from both the prophylactic and therapeutic regimens , and an effect of somewhat greater magnitude from the combination regimen . The combination regimen was associated more with a reduction in severity than frequency of illness , although the extra dosage was limited to the first day of illness . In spite of the eightfold range in daily dose , the three prophylactic-only regimens showed no evidence of a dose-related effect , but the 8 g therapeutic dose was associated with less illness than the 4 g therapeutic dose . There was no evidence of side effects from the 1 and 2 g prophylactic doses of vitamin C , and no evidence of a rebound increase in illness during the month following withdrawal of the daily vitamin supplements . On the basis of this and other studies it is suggested that the optimum daily dose of vitamin C is less than 250 mg , except possibly at the time of acute illness , when a larger daily intake may be beneficial Context Clinical studies of vitamin C as a potential anticancer agent have produced inconsistent results despite in vitro evidence that high concentrations kill cancer cells . Contribution Pharmacokinetic studies in healthy persons , using a depletion-repletion design , show that intravenous administration can achieve 70-fold higher blood levels of vitamin C than the highest tolerated oral dose . Caution s Although this study provides better underst and ing of the pharmacokinetic issues involved in research on vitamin C , it provides no evidence that vitamin C has any effect on cancer cells and can not be used to support its clinical use for therapeutic purpose s. The Editors Vitamin C in gram doses is taken orally by many people and administered intravenously by complementary and alternative medicine practitioners to treat patients with advanced cancer ( 1 , 2 ) . After oral intake ,  vitamin C plasma concentrations are tightly controlled at 70 to 85 mol/L for amounts ( as much as 300 mg daily ) that can be obtained from food ( 3 , 4 ) . However , concentrations achieved by higher pharmacologic doses are uncertain . Despite poor rationale , vitamin C in gram doses was proposed as an anticancer agent decades ago ( 5 ) . Unblinded studies with retrospective or nonr and om controls reported clinical benefit from oral and intravenous vitamin C administered to patients with terminal cancer at a dosage of 10 g daily ( 1 , 6 , 7 ) . Placebo-controlled trials in patients with cancer reported no benefit from oral vitamin C at a dosage of 10 g daily ( 8 , 9 ) , and vitamin C treatment was judged ineffective ( 10 ) . However , in vitro evidence showed that vitamin C  killed cancer cells at extracellular concentrations higher than 1000 mol/L ( 11 , 12 ) , and its clinical use by some practitioners continues . We recognized that oral or intravenous routes could produce substantially different vitamin C concentrations ( 13 ) . We report here that intravenous doses can produce plasma concentrations 30- to 70-fold higher than the maximum tolerated oral doses . These data suggest that the role of vitamin C in cancer treatment should be reexamined , and insights from vitamin C pharmacokinetics can guide its clinical use . Methods Pharmacokinetic Studies in Healthy Persons The study was approved by the Institutional Review Board of the National Institute of Diabetes and Digestive and Kidney Diseases , National Institutes of Health . After we obtained written informed consent , 17 healthy volunteers ( 7 men , 10 women ; age , 19 to 27 years ) were studied as in patients by using a depletion-repletion study design ( 3 , 4 ) . Participants were hospitalized for 3 to 6 months and consumed a  vitamin C-deficient  diet containing less than 0.005 g of vitamin C per day . At plasma vitamin C concentrations less than 8 mol/L , persons were depleted without signs of scurvy . Vitamin C , 0.015 g twice daily , was then administered orally until participants achieved a steady state for this dose ( 0.03 g daily ) . Participants received successive oral daily vitamin C doses of 0.03 g , 0.06 g , 0.1 g , 0.2 g , 0.4 g , 1.0 g , and 2.5 g until a steady state was achieved for each dose . Bioavailability sampling was conducted at a steady state for vitamin C doses of 0.015 g , 0.03 g , 0.05 g 
    Output:
    