title: Vitamin C and the common cold: using identical twins as controls. Ascorbic acid for the common cold. A prophylactic and therapeutic trial. Vitamin C as a preventive medicine against common colds in children. A randomized controlled trial of the therapeutic effect of vitamin C in the common cold. Letter: Vitamin C and the common cold. Therapeutic effect of vitamin C. A co-twin control study. A randomized controlled trial of vitamin C in the prevention and amelioration of the common cold. Vitamin C prophylaxis in marine recruits. Mega-dose vitamin C in treatment of the common cold: a randomised controlled trial. The effects of ascorbic acid and flavonoids on the occurrence of symptoms normally associated with the common cold. Vitamin C supplementation reduces the incidence of postrace symptoms of upper-respiratory-tract infection in ultramarathon runners. L-Ascorbic acid and D-isoascorbic acid in a common cold survey. Trial of ascorbic acid in prevention of colds. Vitamin C and the common cold: a second MZ Cotwin control study. Vitamin C prophylaxis in a boarding school. Large scale studies with vitamin C. The clinical effects of vitamin C supplementation in elderly hospitalised patients with acute respiratory infections. The administration of large doses of ascorbic acid in the prevention and treatment of the common cold. II. Preventing the common cold with a garlic supplement: A double-blind, placebo-controlled survey A trial of ascorbic acid in the treatment of the common cold. A Randomized Controlled Trial for Chemoprevention of Gastric Cancer in High‐risk Japanese Population; Study Design, Feasibility and Protocol Modification Vitamin C and the common cold: a double-blind trial. Vitamin C and upper respiratory illness in Navaho children: preliminary observations (1974). Evaluation of the efficacy of ascorbic acid in prophylaxis of induced rhinovirus 44 infection in man. A co-twin control study of the effects of vitamin C. Does multivitamin supplementation prevent infections in healthy elderly subjects? A controlled trial. The effect on winter illness of large doses of vitamin C. Winter illness and vitamin C: the effect of relatively low doses. Co-twin control studies: vitamin C and the common cold. The beneficial effect of Vitamin C on the common cold Common cold symptomatology and Vitamin C Common cold and vitamin C. The effectiveness of vitamin C in preventing and relieving the symptoms of virus-induced respiratory infections. A controlled clinical trial of ascorbic acid for the common cold. Large-scale trials of vitamin C. 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 % Three hundred eleven employees of the National Institutes of Health volunteered to take 1 gm of ascorbic acid or lactose placebo in capsules three times a day for nine months . At the onset of a cold , the volunteers were given an additional 3 gm daily of either a placebo or ascorbic acid .  One hundred ninety volunteers completed the study . Dropouts were defined as those who missed at least one month of drug ingestion . They represented 44 % of the placebo group and 34 % of those taking ascorbic acid . Analysis of these data showed that ascorbic acid had at best only a minor influence on the duration and severity of colds , and that the effects demonstrated might be explained equally well by a break in the double blind During 7 weeks in the spring of 1973 a double-blind pilot study on 172 children in the age group 8 - 9 was carried out to test the possible effect of 1000 mg vitamin C daily as a prophylactic agent against common colds . During the autumn of 1973 , a main study was carried out on 642 children of the same age . The investigations had the same pattern and lasted for 3 months . Both studies have been processed on the same principles . The results were somewhat divergent but , like previously published studies on children , seemed to indicate that the duration and severity of the cold were reduced while , on the other h and , the incidence remained unaltered or indeed increased . The total number of days of upper respiratory tract infection was smaller for the vitamin C group only in the pilot study ( not in the main study ) . No proven biochemical effects were obtained . Preventive treatment of healthy children with vitamin C in large doses this had no definitely proved effect against colds METHOD A large number of women living in two towns in South Wales , and their husb and s , were asked to cooperate in the trial . These women had been identified several years previously in a study of child growth and nutrition and had already cooperated in a prophylactic trial of vitamin C ( Elwood et al. , 1975 ) . The subjects were visited in September and October and those who agreed were given ten effervescent tablets of either vitamin C ( 1 G ) or an inert ; placebo . Allocation of households to vitamin C or placebo was r and om , but each husb and received the same tablets as his wife . This was done to avoid confusion if tablets were shared . The smoking habit of each subject was recorded . Instructions were given that , when symptoms suggestive of a cold commenced , the tablets were to be started , three tablets per day until the 10 tablets had been taken . Symptoms were to be recorded each day for the duration of the cold . Sufficient detail was requested to enable colds to be classed as ‘ simple ’ , that is nasal symptoms with or without general symptoms such as fever or malaise but without any symptom referable to the chest such as cough . ‘ Chest ’ colds were recorded as any symptom-complex which included cough , wheezing , or other chest symptoms . A stamped addressed envelope was given to each subject for the return of the record card . An arbitrary date was chosen approximately six months after the trial commenced , and any subject who had not returned a A concentration of 15 pig/ml was arbitrarily taken as a level read.ly obtainable in h blood wiLh bo.h antibiotics . Th19 strains resistant to penicillin and tetracycline only were resis : ant to  tetracycline  in concentrations above 20 Ag/lml . This resis ance pattern occurs quite frequently in strains of S. aph . aureus isolated both from hospital patients and from the general comnnunity . It would appear therefore that any microbiological advantage which minocycline may exert over other tetracyclines is due to its sup rior activity against strains of Staph . aureus which are resistant to tetracycline . ' -I am , etc . , ARTHUR A. B. MITCHELL Bacteriology Department , Law Hospital , Carluke , Three different dosages of vitamin C , dependent on body weight , were administered to 44 school-aged monozygotic twins for five months using a double-blind , co-twin control study design . The mothers recorded daily observations of cold symptoms , and multiple biochemical , anthropometric , and psychological measurements were made at the beginning and end of the study . Paired comparisons showed no significant overall treatment effect on cold symptoms , but the response was not uniform in all sub-groups . Treated girls in the youngest two groups had significantly shorter and less severe illness episodes , and an effect on severity was also observed in the youngest group of boys . The seven treated twins in the latter group also grew an average of 1.3 cm more than their untreated co-twins during the five-minth period of the study 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 A prospect i ve , r and omized , double-blind study was carried out to determine whether vitamin C prophylaxis , 2.0 g/day , vs placebo prophylaxis would reduce the incidence or morbidity of the common cold  and other respiratory illnesses in 674 marine recruits during an eight-week period . Whole-blood ascorbic acid levels measured six weeks after initiation of the study were significantly higher in the vitamin C group . There was no difference between the two groups in the incidence or duration of colds . The vitamin C group rated their colds as being less severe , but this was not reflected in different symptom complexes or in fewer sick-call visits or training days lost . This study and the literature do not support the prophylactic use of vitamin C to prevent the common cold 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 A controlled study was made of the effects of natural orange juice , synthetic orange juice , and placebo in the prevention of the common cold ; both natural and synthetic orange juices contained 80 mg of ascorbic acid daily . Three-hundred sixty-two healthy normal young adult volunteers , ages 17 to 25 years , were studied for 72 days with 97 % of participants completing the trial . There was a 14 to 21 % reduction in total symptoms due to the common cold in the supplemented groups that was statistically significant ( P less than 0.05 ) . Ascorbic acid supplementation also increased the number of " episode-free " subjects . However , the clinical usefulness of the results does not support prophylactic ascorbic acid supplements in the well-nourished adult . The results in this study with both natural and synthetic orange juice of physiological content of ascorbic acid , are similar to those obtained using a " megadose " of ascorbic acid This study determined whether daily supplementation with 600 mg vitamin C would reduce the incidence of symptoms of  upper-respiratory-tract ( URT ) infections after participation in a competitive ultramarathon race ( > 42 km ) . Ultramarathon runners with age-matched controls were r and omly divided into placebo and experimental ( vitamin C-supplemented ) groups . Symptoms of URT infections were monitored for 14 d after the race . Sixty-eight percent of the runners in the placebo group reported the development of symptoms of URT infection after the race ; this was significantly more ( P < 0.01 ) than that reported by the vitamin C-supplemented group ( 33 % ) . The duration and severity of symptoms of URT infections reported in the vitamin C-supplemented nonrunning control group was also significantly less than in the nonrunning control group receiving the placebo ( P < 0.05 ) . This study provides evidence that vitamin C supplementation may enhance resistance to the postrace URT infections that occur commonly in competitive ultramarathon runners and may reduce the severity of such infections in those who are sedentary 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 Ascorbic acid is widely used as a prophylactic and therapeutic agent against the common cold , and is in fact often recommended for this purpose by medical practitioners . It may be administered as a large dose as soon as possible after the first symptoms are felt , and this dosage is then continued for a few days in order to " abort " the cold . Though many people use this treatment on themselves and believe it is effective , it is impossible to assess its efficacy . Untreated subjects may experience symptoms such as sneezing or a mild sore throat , which then disappear without going on to a full cold , and patients ' assessment s of their colds are much influenced by any treatment owing to the placebo effect ( Diehl et a/. , 1938 ) . In these studies we attempted to show by in-vitro experiments that exposure of cells to ascorbic acid increased their resistance to infection with viruses . Though there was no activity in vitro , we also attempted to demonstrate a protective effect in ftnmy»1 « or man , since it was thought that host resistance might be enhanced indirectly 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 The combination of a regular daily supplement of vitamin C with extra dosage at the time of illness has been shown to reduce the disability due to common colds and other winter illness , but we have seen little effect on frequency of infections , sense of ( well-being ) , or levels of serum cholesterol . The variable results that have been obtained from some other trials of vitamin C may be due in part to variation in the initial nutritional state of the subjects , with the greatest effects to be expected where there is most room for improvement . Because of the great variation in individual susceptibility to infection large numbers of subjects are required in these trials and they must be strictly double-blind . Although we have seen no clear evidence of harmful side-effects , occasional sensitivity to large doses of vitamin C can not be ruled out , and the withdrawal depression of blood levels could conceivably interfere with a patient 's ability to h and le stress A r and omised double-blind trial involving vitamin C/placebo supplementation was conducted on 57 elderly patients admitted to hospital with acute respiratory infections ( bronchitis and bronchopneumonia ) . Patients were assessed clinical ly and biochemically on admission and again at 2 and 4 weeks after admission having received either 200 mg vitamin C per day , or placebo . This relatively modest oral dose led to a significant increase in plasma and white cell vitamin C concentration even in the presence of acute respiratory infection . Using a clinical scoring system based on major symptoms of the respiratory condition , patients supplemented with the vitamin fared significantly better than those on placebo . This was particularly the case for those commencing the trial most severely ill , many of whom had very low plasma and white cell vitamin C concentrations on admission . Various mechanisms by which vitamin C could assist this type of patient are discussed Beginning at about the age of seven and following a tonsillectomy I began to be plagued with otitis media of which I suffered from 50 to 60 bouts over the next 20 years . These recurrent infections were treated by a series of different methods including Cubeb cigarette smoke blown into the ear by my mother , the local application of heat , sulfadiazine in nasal sprays and the earlier and later forms of injected penicillin which was useful as soon as I suffered from a sore throat if taken at the first signs of infection , but only for the secondary bacterial component of my double infection which began with a vims which appeared to pass the sentence which was executed by the bacteria . I stumbled upon the employment of ascorbic acid because of the advertisements for the bioflavonoids and vitamin C as beneficial in the prevention - and treatment of the common cold . It was apparent that the mixture diminished the symptoms of the common cold for me and for my wife , but not enough for us to continue with its employment , Would larger doses perhaps be more effective ? The doses were increased as each increment proved itself as giving better results until I reached a maximum and satisfactory effect . I did not permit myself to be dissuaded by the gloomy conclusions of others , whose work I continued to recognize had shown only that vitamin C had not been helpful against colds at the dosage used in their studies , and not the unmeasured generality that this drug had been proven utterly useless against colds . I was then able to suppress colds , at will , in five subjects . There is no doubt that we really suffered from colds during these suppressed versions of the disease , because we continued to be aware — but just aware — of whatever symptoms had been characteristic of our formerly unmodified colds . Although running of the nose would be practically non-existent , on rare occasions a single drop might appear at the nares ; however , not -a trace of " itchiness " had accompanied it in its roll down the turbinates . The thickened stage of nasal discharge was never reached . Sneezing and coughing were quite unusual . A throat did not proceed to " soreness " but , in some cases , there was a slight sensation of its presence . Hoarseness was uncommon . Headache was inconsequential . Malaise , if at all recognizable was usually so minor as to be undeserving of the name . Secondary bacterial invasions did not occur . I learned that the treatment had to be initiated early enough and needed to be continued at a high level for some time and then withdrawn or One hundred forty-six volunteers were r and omized to receive a placebo or an allicin-containing garlic supplement , one capsule daily , over a 12-week period between November and February . They used a five-point scale to assess their health and recorded any common cold infections and symptoms in a daily diary . The active-treatment group had significantly fewer colds than the placebo group ( 24 vs 65,P < .001 ) . The placebo group , in contrast , recorded significantly more days challenged virally ( 366 vs 111,P < .05 ) and a significantly longer duration of symptoms ( 5.01 vs 1.52 days , P < .001 ) . Consequently , volunteers in the active group were less likely to get a cold and recovered faster if infected . Volunteers taking placebo were much more likely to get more than one cold over the treatment period . An allicin-containing supplement can prevent attack by the common cold virus 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 We have initiated a population ‐based , double‐blind , r and omized controlled trial to examine the effects of supplementation of beta‐carotene and vitamin C on the incidence of  gastric cancer . The subjects were participants in an annual health screening program conducted by four municipalities in Akita prefecture , one of the regions with the highest mortality from gastric cancer in Japan . We measured their serum levels of pepsinogens ( PGs ) I and II , and asked persons diagnosed with chronic atrophic gastritis ( defined as PGI < 70 ng/ml and PGI/PGII ratio < 3.0 ) to take diet supplements containing 0 or 15 mg/day beta‐carotene and 50 or 500 mg/day vitamin C for 5 years . During the first year of recruitment conducted in one village from June through September , 1995 , 52 % ( 635/1214 ) of screening participants had chronic atrophic gastritis and 73 % ( 439/602 ) of eligible persons responded . However , in response to a National Cancer Institute press report released on January 18 , 1996 , indicating that two beta‐carotene trials had shown no benefit and potential harm from the supplement , we discontinued the beta‐carotene and continued with the trial using only vitamin C.  Of 397 participants remaining at this point , 77 % ( 305 ) consented to stay in the study . The results indicate that a r and omized controlled trial for cancer prevention is feasible in the Japanese asymptomatic population 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 Twenty-one healthy , susceptible adult male volunteers were enrolled in a doubleblind study design ed for evaluation of the prophylactic efficacy of ascorbic acid ( 3 g daily ) in induced rhinovirus 44 infection of the upper respiratory tract . While in continuous isolation , 11 men received 1 g of ascorbic acid three times daily , and 10 men received a placebo for two weeks , after which an intranasal inoculum containing 100 TCID50 of rhinovirus 44 was administered . Each man continued to receive the same dose of medication for one week after the viral challenge . All participants subsequently developed typical illness due to rhinovirus . Similar levels of antibody in serum , nasal washings , and sputum developed in all subjects . Nasal shedding of virus and the flow of the nasal mucociliary blanket were unaffected by the ingestion of ascorbic acid . No prophylactic benefit was demonstrated from the daily ingestion of 3 g of ascorbic acid in induced rhinovirus 44 infection in man . Viral infections of the respiratory tract are the most common illness affecting mankind . The mortality from these afflictions is low , but the morbidity , when assessed as discomfort and time lost from gainful employment and leisure pursuits , is high . Therefore , it is critical to assess the controversial cl aims for the efficacy of ascorbic acid ( vitamin C ) for the prevention and relief of colds [ 1 - 5 ] . The need for a further study of the possible role of ascorbic acid in the prophylaxis and therapy of viral infections of the respiratory tract under carefully controlled circumstances was evident In recent years , a number of benefits of prophylactic pharmacologic doses of vitamin C have been suggested . In addition to cl aims by Linus Pauling [ 1971 ] and others of a reduction in the morbidity due to the common cold and upper respiratory infections , other authors have subsequently suggested that serum cholesterol levels may be lowered [ Spittle , 1971 ] . Some investigations have suggested that this effect may be observed only in hypercholesterolemic individuals and not those with normal cholesterol levels [ Sokoloff et al , 1966 ; Ginter et al , 1970 ] . It has also been suggested that exogenous vitamin C might improve mental alertness as measured by IQ test performance [ Kubala and Katz , 1960 ] . The present study was design ed to test these hypotheses by means of a double-blind co-twin control study We performed a double blind r and omized study in order to assess the efficacy of a multivitamin supplement for the prevention of common infections in healthy elderly subjects . Non-institutionalized , independent subjects over 60 years of age , living in the Nevers area ( central France ) were recruited by announcements and r and omly assigned to a treatment or a placebo group . The treatment or placebo tablets were to be taken daily for 4 months . The principal criterion of response was the incidence of infections , as recorded from a detailed question naire presented at entrance , in the middle ( 2 months ) and at the end ( 4 months ) of the study . Blood sample s were taken at the entrance in the study and after two and four months in order to monitor vitamin status . No significant difference was found between the two groups for the incidence of infections . In fact the observed incidences during the two two-month periods were higher in the treatment ( 0.38 and 0.21 ) than in the placebo group ( 0.29 and 0.13 ) . After two months and after four months of supplementation , blood vitamin indicators of the subjects were significantly higher in the treatment than in the placebo group for vitamins B1 , B2 , B6 , E and folates ( p < 0.001 ) . The improvement of the vitamin C status was slightly higher in the treatment than in the placebo group . For vitamin A status , the evolution was similar in the two groups . In conclusion , short-term supplementation of healthy elderly subjects with the investigated supplement is not likely to afford a meaningful protection against common infections 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 After their r and om -llocation to one of three treatment aroups , 622 volunteers received either  vitamin C or placebo in a maintenance dose of 500 mg once weekly and a therapeutic dose of 1500 mg daily on the 1st day and 1000 mg on the next 4 days of any illness . Two forms of vitamin C were employed : a sustained-release capsule containing ascorbic acid and a regular tabet containing a mixture of sodium and calcium ascorbate . In the 448 subjects who completed an average of 15 weeks in the study of total of 635 episodes of illness were recroded . Respiratory symptoms were recorded on at least 1 day in 92 per cent of these episodes . There were no consistent or significant differences in the sickness experience of the subjects receiving the sustained-release vitamin capsules compared to those receiving the vitamin tablets , but subjects in both vitamin groups experienced less severe illness than subjects in the placebo group , with approximately 25 per cent fewer days spent indoors because of the illness ( P smaller than 0.05 ) . These results are compatible with the belief that supplementary vitamin C can reduce the burden of winter illness , but the intake need not be as high as has sometimes been cl aim ed 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 Summary The occurrence of common cold symptoms was recorded daily for a period of nine months by children from two male and two female boarding schools . All the children in one male and one female school received tablets containing 200 mg Vitamin C , or placebo tablets , daily on a double blind basis . Children in the other two schools received 200 or 500 mg tablets of Vitamin C.  Leucocyte ascorbic acid concentrations were significantly raised in those children receiving active tablets . Comparisons of incidence , duration , severity and total intensity of cold characteristics , and of cold frequencies , were made between the different treatment groups . Cold symptoms were grouped into those characteristic of Catarrhal ( C-colds ) , and those of Toxic ( T-colds ) , colds . Whole ( W-colds ) consisted of at least one C-symptom in combination with one or more T-symptoms . 200 mg of Vitamin C had a beneficial effect on severity and total intensity of C- and W-colds , but did not affect T-colds , in girls . 500 mg produced further slight beneficial effects . With 200 mg the cold categories in boys tended to show a deterioration , and the deterioration continued in the group receiving 500 mg . Analysis of cold frequency indicated that T-colds are commoner in girls . Their C-cold frequency diminished with the smaller dose , and their T-cold frequency was reduced by the larger dose of Vitamin C. In boys C-cold frequency diminished with 500 mg of Vitamin C daily . These data suggest that there is a sexual difference in the effects of Vitamin C on the characteristics of the common cold . Evaluation of the effects of Vitamin C on toxic and catarrhal symptoms in relation to administered doses is of more importance than examination of its prophylactic or therapeutic actions . 500 mg had some beneficial effect in girls : any beneficial effect of Vitamin C on the common cold in boys will probably be associated with administration of a higher daily dose Summary The occurrence and severity of nine symptoms of the common cold were recorded daily for 35 weeks by girls and boys in four Dublin boarding schools . Half the children in each school received placebo or 200 mg tablets , or 200 mg or 500 mg tablets , of Vitamin C daily on a double blind basis . Diets or environmental conditions did not differ between the schools . A score for the severity of each symptom was obtained daily for all the subjects throughout the trial in the different treatment groups . The degree of association between pairs of symptoms was calculated . The symptoms of the common cold syndrome ( the W-complex ) tended to exist in two groups defined as Toxic and Catarrhal complexes ( T- and C-complexes ) . The intensity and quality of W-complex symptoms were assessed in terms of the correlation value above which the constituent T- and C-complexes became manifest , the average correlation values of the constituent complexes , and the linkage of the symptoms in these complexes . The values for , and quality of , the complexes were dependent on the sex of the sample s and the dose of Vitamin C administered . Boys tended to have more complicated W-complexes which broke down into T- and C-complexes with the lower dose of Vitamin C. These became more complicated when increasing doses of Vitamin C were administered . Girls had less complicated W-complexes , but more complicated T- and C-complexes , than boys . Increasing doses of Vitamin C made the girls ' T- and C-complexes less complicated . Administration of Vitamin C appeared to benefit the common cold syndrome more in girls than in boys Abstract The effect of daily administration of placebo or 200 or 500 mg . tablets of vitamin C on symptom association and on the incidence , duration , severity , and total intensity of the symptoms  in the common cold has been studied . The metabolism of ascorbic acid during the common cold , and after disappearance of all the symptoms , has been investigated by examining the plasma and leucocyte ascorbic-acid concentrations after a loading dose of 500 mg . vitamin C. Cold symptoms tend to dissociate into toxic and catarrhal complexes , the complexity and frequency of which differ between boys and girls .  Vitamin C reduces symptom association and alters the frequency of toxic and catarrhal complexes . It significantly reduces the severity and total intensity of colds in girls , but does not benefit cold symptoms in boys at a daily dose of 500 mg . During colds , especially of the catarrhal variety , ascorbic acid is transferred out of the leucocytes into the plasma , where it is rapidly metabolised in both sexes , but this effect is more pronounced in females . There is a significant positive correlation between metabolic utilisation of ascorbic acid during colds and intensity of cold symptoms BACKGROUND An ever increasing dem and to evaluate the effect of dietary supplements on specific health conditions by use of a " significant scientific " st and ard has prompted the publication of this study . OBJECTIVE To study the effect of megadose Vitamin C in preventing and relieving cold and flu symptoms in a test group compared with a control group . DESIGN Prospect i ve , controlled study of students in a technical training facility . SUBJECTS A total of 463 students ranging in age from 18 to 32 years made up the control group . A total of 252 students ranging in age from 18 to 30 years made up the experimental or test group . METHOD Investigators tracked the number of reports of cold and flu symptoms among the 1991 test population of the facility compared with the reports of like symptoms among the 1990 control population . Those in the control population reporting symptoms were treated with pain relievers and decongestants , whereas those in the test population reporting symptoms were treated with hourly doses of 1000 mg of Vitamin C for the first 6 hours and then 3 times daily thereafter . Those not reporting symptoms in the test group were also administered 1000-mg doses 3 times daily . RESULTS Overall , reported flu and cold symptoms in the test group decreased 85 % compared with the control group after the administration of megadose Vitamin C. CONCLUSION Vitamin C in megadoses administered before or after the appearance of cold and flu symptoms relieved and prevented the symptoms in the test population compared with the control group Vitamin C has been a popular medication for preventing the common cold and reducing the severity of cold symptoms for many years . - ' Professor Pauling 's recent book on the subject has led to even further use of vitamin C in even larger doses . This study was performed to look for a difference in the frequency and severity of colds in a generally healthy , middle-class , medically aware population of employees at the National Institutes of Health . High doses of vitamin C were used for both prevention and treatment ; virus isolations were attempted in an effort to relate viral types to vitamin C response ; and the study was continued for a nine-month period in an attempt to examine seasonal variations of viruses and colds . The study was conducted so that nurses , physicians , and volunteers did not know who received placebo and who received ascorbic acid . Only the consulting statistician and the pharmacist could relate patient code numbers to medication received . Progress was monitored by a research committee not connected with the day-to-day activities 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 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: Vitamin C in doses as high as one gram daily for several winter months , had no consistent beneficial effect on incidence of the common cold .
  For both preventive and therapeutic trials , there was a consistently beneficial but generally modest therapeutic effect on duration of cold symptoms .
  There was no clear indication of the relative benefits of different regimes or vitamin C doses .
  However in trials that tested vitamin C after cold symptoms occurred , there was some evidence that a large dose produced greater benefits than lower doses .
  REVIEW ER 'S CONCLUSIONS Long term daily supplementation with vitamin C in large doses daily does not appear to prevent colds .
background: BACKGROUND The role of oral ascorbic acid ( vitamin C ) in the prevention and treatment of colds remains controversial despite many controlled trials .
  There have also been a number of efforts to synthesize and /or overview the results of these trials , and controversy over what these overviews tell us .
  OBJECTIVES The objective of this review was to answer the following two questions : ( 1 ) Does regular high dosage supplementation with vitamin C reduce the incidence of colds ? (
  2 ) Does taking vitamin C in high doses at the onset of a cold have a therapeutic effect ?