title: Vitamin C and the common cold: using identical twins as controls. A randomized controlled trial of vitamin C in the prevention and amelioration of the common cold. Mega-dose vitamin C in treatment of the common cold: a randomised controlled trial. L-Ascorbic acid and D-isoascorbic acid in a common cold survey. Vitamin C and the common cold: a second MZ Cotwin control study. Vitamin C prophylaxis in a boarding school. A randomised controlled trial of the effect of the provision of free school milk on the growth of children. A trial of ascorbic acid in the treatment of the common cold. Vitamin C and the common cold: a double-blind trial. Vitamin C and upper respiratory illness in Navaho children: preliminary observations (1974). The effect on winter illness of large doses of vitamin C. Vitamin C Pharmacokinetics: Implications for Oral and Intravenous Use Co-twin control studies: vitamin C and the common cold. Vitamin C pharmacokinetics in healthy volunteers: evidence for a recommended dietary allowance. Vitamin C supplementation in normal subjects reduces constitutive ICAM-1 expression. Large-scale trials of vitamin C. Vitamin C and acute illness in Navajo school children. Ascorbic acid and the common cold. Evaluation of its efficacy and toxicity.
abstract: 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 , 0.1 g , 0.2 g , 0.5 g , and 1.25 g. For each bioavailability sampling , vitamin C was administered in the fasting state . After oral administration , blood sample s were collected at 0 , 15 , and 30 minutes and at 1 , 1.5 , 2 , 2.5 , 3 , 3.5 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 19 , 22 , and 24 hours ( 3 , 4 ) . After intravenous administration at 250 mg/min , blood sample s were collected at 0 , 2.5 , 5 , 10 , 15 , and 30 minutes and at 1 , 1.5 , 2 , 2.5 , 3 , 3.5 , 4 , 5 , 6 , 7 , 8 , 9 , and 10 hours . Data obtained from bioavailability samplings were used to determine peak plasma and urine vitamin C concentrations . Pharmacokinetic Modeling We used data from 7 men to construct a unique 3-compartment vitamin C pharmacokinetic model with parameters describing saturable absorption , tissue distribution , and renal excretion and reabsorption ( 14 ) . This model was used to predict peak plasma and urine vitamin C concentrations attained when pharmacologic doses of the vitamin are administered . For intravenous administration , it was assumed that vitamin C was infused at a rate of 1 g/min , and urine output was 100 mL/h . Vitamin C Assay Vitamin C was measured by using high-performance liquid chromatography with coulometric electrochemical detection ( 3 , 4 , 15 ) . Statistical Analysis We compared plasma vitamin C concentration curves ( against either dose or time ) by repeated- measures analyses of variance ( ANOVA ) . In addition to the repeating factor ( dose or time ) , other factors considered were sex and route of administration . In the comparison of routes of administration at multiple doses , in which sex not only was an important factor itself but also had an important interaction with route , separate ANOVA were determined for men and women to assess the importance of route of administration . Analyses were performed by using Data Desk , version 5 ( 1995 ) ( Data Description , Inc. , Ithaca , New York ) . Role of the Funding Source The funding source had no role in the design , conduct , and reporting of the study or in the decision to su bmi t the manuscript for publication . Results When 1.25 g of vitamin C was given intravenously , plasma concentrations were significantly higher than when the vitamin was given orally ( P < 0.001 by repeated- measures ANOVA ) ( Figure 1 ) . In addition , plasma concentrations were significantly higher over all doses ( P < 0.001 by repeated- measures ANOVA ) with intravenous compared with oral administration ( Figure 1 , inset ) . At the highest dose of 1.25 g , mean peak values from intravenous administration were 6.6-fold higher than mean peak values from oral administration . When all doses were considered , peak plasma vitamin C concentrations increased with increasing intravenous doses , whereas peak plasma vitamin C concentrations seemed to plateau with increasing oral doses . Urine vitamin C concentrations were higher for the same dose given intravenously compared with that administered by the oral route . At the highest dose of 1.25 g , peak urine concentrations from intravenous administration were approximately 3.5 times higher than from oral administration ( data not shown ) . Figure 1 . Plasma vitamin C concentrations in healthy volunteers after intravenous or oral administration of vitamin C. Inset : The 3-compartment vitamin C pharmacokinetic model that we developed predicted that a single oral dose of 3 g , the maximum tolerated single dose , produced a peak plasma concentration of 206 mol/L ( Figure 2 , top ) . Peak predicted concentration after a single 1.25-g oral dose was slightly lower at 187 mol/L. For 200 mg , an amount obtained from vitamin C-rich foods , peak predicted concentration was approximately 90 mol/L. Plasma concentrations for all of these amounts returned to steady-state values , approximately 70 to 85 mol/L , after 24 hours . With 3 g given orally every 4 hours , the maximum tolerable ( 6 ) , peak predicted plasma concentration was approximately 220 mol/L ( Figure 2 , top ) . By contrast , after intravenous administration , predicted peak plasma vitamin C concentrations were approximately 1760 mol/L for 3 g , 2870 mol/L for 5 g , 5580 mol/L for 10 g , 13 350 mol/L for 50 g , and 15 380 mol/L for 100 g ( Figure 2 , bottom ) . Doses of 60 g given intravenously are used for cancer treatment by complementary and alternative medicine practitioners ( 2 ) . Predicted peak urine vitamin C concentrations were as much as 140-fold higher after intravenous administration compared with oral administration ( data not shown ) . Figure 2 . Predicted plasma vitamin C concentrations in healthy persons after oral ( top ) or intravenous ( IV ) ( bottom ) administration of vitamin C. Discussion Our data show that vitamin C plasma concentrations are tightly controlled when the vitamin is taken orally , even at the highest tolerated amounts . By contrast , intravenous administration bypasses tight control and results in concentrations as much as 70-fold higher than those achieved by maximum oral consumption . Both findings have clinical relevance . Vitamin C oral supplements are among the most popular sold , and gram doses are promoted for preventing and treating the common cold , managing stress , and enhancing well-being ( 1 ) . Our data show that single supplement gram doses produce transient peak plasma concentrations that at most are 2- to 3-fold higher than those from vitamin C-rich foods ( 200 to 300 mg daily ) . In either case , plasma values return to similar steady-state concentrations in 24 hours . Because differences in plasma concentrations from supplements and from food intake are not large , supplements would be expected to confer little additional benefit , a finding supported by available evidence ( 16 , 17 ) . However , consumption of fruits and vegetables , which contain vitamin C , is beneficial for unknown reasons ( 16 , 17 ) . On the basis of current knowledge and the pharmacokinetics presented here , physicians should advise their patients to consume fruits and vegetables , not vitamin C supplements , to obtain potential benefits . Just as important , our data show that intravenous administration of vitamin C produces substantially higher plasma concentrations than can be achieved with oral administration of vitamin C. This difference was previously unrecognized and may have treatment implication s. Case series published by Cameron , Campbell , and Pauling ( l , 6 , 7 ) have been controversial . In these series , several hundred patients with terminal cancer treated with 10 g of vitamin C intravenously for 10 days and then 10 g orally indefinitely were compared with more than 1000 retrospective and prospect i ve controls . Patients treated with vitamin C  survived 150 to 300 days longer than controls ( 1 , 6 , 7 ) . Other research ers reported benefit consisting of increased survival , improved well-being , and reduced pain ( 1 ) . All of these Jtending to make one pair different from another , so providing a more efficient test of the treatment effect . The increase in efficiency of the matched pair over the r and om group design is dependent upon the extent to which the matching has removed extraneous factors influencing the effect of the drug . The ultimate matched pair in human experimentation is a pair of monozygotic ( MZ ) twins who have been reared together . Not only is there a perfect match for age , sex , and family background but , perhaps most importantly , genetic constitution is identical , at least for nuclear genes . The paired and unpaired design s are shown in Table I and have been compared extensively by Christian and Kang [ 1972 ] . The paired analysis allows the partition of variance between individuals ( 0111 ) into that between pairs ( oip ) and that within pairs ( a2 wp ) . For sufficiently large N , if oip > 0 ( ie , if the between-pairs mean square is significantly greater than the pairs x treatments mean square ) , then the paired design will give a more powerful test of the between-treatments effect than the unpaired design . For the num­ bers we have here , it may be shown that oi1/a2 wp is the multiplier to estimate how many more pairs of unrelated individuals would be needed to provide a test of the between-treatments effect of the same power as is provided by a given number of pairs of twins Determinants of the recommended dietary allowance ( RDA ) for vitamin C include the relationship between vitamin C dose and steady-state plasma concentration , bioavailability , urinary excretion , cell concentration , and potential adverse effects . Because current data are inadequate , an in-hospital depletion-repletion study was conducted . Seven healthy volunteers were hospitalized for 4 - 6 months and consumed a  diet  containing  < 5 mg of vitamin C daily .  Steady-state plasma and tissue concentrations were determined at seven daily doses of vitamin C from 30 to 2500 mg .  Vitamin C steady-state plasma concentrations as a function of dose displayed sigmoid kinetics . The steep portion of the curve occurred between the 30- and 100-mg daily dose , the current RDA of 60 mg daily was on the lower third of the curve , the first dose beyond the sigmoid portion of the curve was 200 mg daily , and complete plasma saturation occurred at 1000 mg daily . Neutrophils , monocytes , and lymphocytes saturated at 100 mg daily and contained concentrations at least 14-fold higher than plasma . Bioavailability was complete for 200 mg of vitamin C as a single dose . No  vitamin C  was excreted in urine of six of seven volunteers until the 100-mg dose . At single doses of 500 mg and higher , bioavailability declined and the absorbed amount was excreted . Oxalate and urate excretion were elevated at 1000 mg of vitamin C daily compared to lower doses . Based on these data and Institute of Medicine criteria , the current RDA of 60 mg daily should be increased to 200 mg daily , which can be obtained from fruits and vegetables . Safe doses of vitamin C are less than 1000 mg daily , and vitamin C daily doses above 400 mg have no evident value Regulation of monocyte adhesion molecule gene expression is via redox sensitive transcription factors . We have investigated whether dietary antioxidant supplementation with vitamin C ( 250 mg/day ) can modulate monocyte ICAM-1 expression in healthy male subjects with low plasma vitamin C at baseline . In a r and omised , double-blind , crossover study , monocyte ICAM-1 mRNA was analysed using quantitative reverse transcriptase PCR . Protein was determined by flow cytometry ( monocytes ) and ELISA ( plasma ) . Monocyte numbers were unaltered by supplementation . Subjects with low plasma vitamin C ( < 50 microM ) prior to supplementation expressed higher levels of monocyte ICAM-1mRNA , and showed a significant ( 50 % ) reduction in ICAM-1mRNA expression after 6 weeks of 250 mg/day vitamin C supplementation ( p<0.05 ) . This was paralleled by a reduction in sICAM-1 ( p<0.05 ) . For the first time , these results show that dietary vitamin C can modulate monocyte ICAM-1 gene expression in vivo , where regulation of gene expression represents a novel mechanism for benefit from dietary antioxidants Among the many cl aims made about the value of large doses of vitamin C , those relating to the prevention and treatment of " colds " have aroused most interest , and the first question to be answered is whether there is any real evidence that such an effect exists , or whether the cl aims are based entirely on wishful thinking . If there is no good evidence of an effect , then there is little point in pursuing the matter . If , on the other h and , the evidence suggests that there is some sort of effect , a host of secondary questions present themselves : ( 1 ) Is the effect specific for the common-cold group of viruses , or is it a more general anti-infective ( or even antistress ) effect ? ( 2 ) Is it a reflection of an increased metabolic need in certain individuals or at certain times , or is it a pharmacological action unrelated to the normal metabolic function of ascorbic acid ? ( 3 ) Is the beneficial effect related to a regular daily intake ( " prophylactic " ) or to extra intake during the course of an illness ( " therapeutic " ) or to a com bination of both ? ( 4 ) Are large doses really necessary , or could equally good results be ob tained with a more moderate supplementation of normal dietary intake ? ( 5 ) If large doses are necessary , does the risk of side effects outweigh the possible benefits ? From a practical point of view it is this last question that most urgently needs to be answered . Further , since it seems reasonable to suppose that side effects are more likely to appear with higher doses and with prolonged intake , the first point to establish is whether there is any value to the regular " prophylactic " use of large doses of vitamin C , and whether in fact the size of the daily dose is as important as has been cl aim ed . In passing , it may be noted that although we have seen no symptomatic evidence of toxicity result ing from doses of up to 2000 mg daily over three or four months in healthy persons , this does not mean that this dose level is necessarily safe for longer periods , particularly in individuals with preexisting disease , or that the occasional individual might not show some unusual and undesirable reaction . Furthermore , while perhaps not a side effect in the ordinary sense of the word , the depression in blood ascorbate levels that occurs on sudden withdrawal of a chronic high intake should be recognized as a potentially harmful reaction . For example , an individual admitted to the hospital with an acute medical or surgical condition might be at a physiological disadvantage if this period of unusual stress coincided with an acute  hypoascorbemia  due to sudden withdrawal of a regular high intake . What then , is the evidence regarding the prophylactic use of large doses of vitamin C ? There is , of course , a great deal of anecdotal evidence , but this is of dubious value because of the well-recognized interaction between mental To evaluate earlier observations , including our own , showing usefulness of vitamin C for managing the common cold , we performed a double-blind trial of vitamin C versus placebo in 868 children . There was no difference in number becoming ill ( 133 versus 129 ) , number of episodes ( 166 versus 159 ) or mean illness duration ( 5.5 versus 5.8 days ) between the groups . Children receiving vitamin C  had fewer throat cultures yielding beta-hemolytic streptococcus ( six versus 13 , P less than 0.10 ) , but no difference in overall complicated illness rate ( 24 versus 25 ) . Plasma ascorbic acid levels were higher in the vitamin group 24 to 26 hours after supplementation ( 1.28 versus 1.04 mg per 100 ml , P less than 0.01 ) . Children with high plasma ascorbic acid concentrations had longer mean illness ( 6.8 versus 4.0 days , P less than 0.05 ) than those with low levels . Vitamin C does not seem to be an effective prophylactic or therapeutic agent for upper respiratory illness We review ed the clinical data relating to the efficacy and safety of pharmacologic doses of ascorbic acid in the prevention and treatment of the common cold .  Although one study tentatively supports the hypothesis that such doses of ascorbic acid may be efficacious , a second study by the same group did not confirm the significant findings , and no clear , reproducible pattern of efficacy has emerged from the review of all the evidence . Similarly , there is currently little adequate evidence on either the presence or the absence of serious adverse reactions to such doses of ascorbic acid , although many such reactions have been hypothesized . The unrestricted use of ascorbic acid for these purpose s can not be advocated on the basis of the evidence currently available
target: 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 .
background: BACKGROUND The role of oral vitamin C ( ascorbic acid ) in the prevention and treatment of the  common cold  has been a subject of controversy for at least sixty years .
  Public interest in the topic continues to be high and vitamin C continues to be widely sold and used as a preventive and therapeutic agent for this common ailment .
  OBJECTIVES To discover whether oral vitamin C in doses of 200 mg or more daily , reduces the incidence , duration or severity of the common cold when used either as continuous prophylaxis or after the onset of cold symptoms .