A controlled clinical trial of ascorbic acid for the common cold. Large-scale trials of vitamin C. Common cold and vitamin C. The beneficial effect of Vitamin C on the common cold Vitamin C prophylaxis in marine recruits. A randomized controlled trial of vitamin C in the prevention and amelioration of the common cold. The administration of large doses of ascorbic acid in the prevention and treatment of the common cold. II. Vitamin C and acute illness in Navajo school children. Evaluation of the efficacy of ascorbic acid in prophylaxis of induced rhinovirus 44 infection in man. Mega-dose vitamin C in treatment of the common cold: a randomised controlled trial. Vitamin C and upper respiratory illness in Navaho children: preliminary observations (1974). Vitamin C as a preventive medicine against common colds in children. Trial of ascorbic acid in prevention of colds. Ascorbic acid for the common cold. A prophylactic and therapeutic trial. Vitamin C and the common cold: a second MZ Cotwin control study. Effects of Three‐month Oral Supplementation of β‐Carotene and Vitamin C on Serum Concentrations of Carotenoids and Vitamins in Middle‐aged Subjects: A Pilot Study for a Randomized Controlled Trial to Prevent Gastric Cancer in High‐risk Japanese Population Vitamin D Supplementation and the Risk of Colds in Patients with Asthma. Large scale studies with vitamin C. The effectiveness of vitamin C in preventing and relieving the symptoms of virus-induced respiratory infections. Regular vitamin C supplementation during pregnancy reduces hospitalization: outcomes of a Ugandan rural cohort study Vitamin C and the common cold: a double-blind trial. Preventing the common cold with a vitamin C supplement: A double-blind, placebo-controlled survey The Women's Health Initiative calcium-vitamin D trial: overview and baseline characteristics of participants. Ascorbic acid and the common cold. Evaluation of its efficacy and toxicity. Maternal vitamin D supplementation during pregnancy A trial of ascorbic acid in the treatment of the common cold. The effects of ascorbic acid and flavonoids on the occurrence of symptoms normally associated with the common cold. The vitamin E debate: implications for ongoing trials of pre‐eclampsia prevention A randomized controlled trial of the therapeutic effect of vitamin C in the common cold. Effect of a dietary supplement containing probiotic bacteria plus vitamins and minerals on common cold infections and cellular immune parameters. L-Ascorbic acid and D-isoascorbic acid in a common cold survey. Vitamin E and respiratory tract infections in elderly nursing home residents: a randomized controlled trial. Routine Vitamin Supplementation To Prevent Cancer and Cardiovascular Disease: Recommendations and Rationale Vitamin C and E supplementation in women at risk of preeclampsia is associated with changes in indices of oxidative stress and placental function. Common cold symptomatology and Vitamin C Therapeutic effect of vitamin C. A co-twin control study.
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 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 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 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 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 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 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 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 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 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 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 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 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 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 Prior to a r and omized controlled trial to prevent gastric cancer by oral supplementation of β‐carotene and vitamin C in a high‐risk Japanese population , we examined the serum response to threemonth oral supplementation of β‐carotene ( 0 , 3 , 30 mg/day ) and vitamin C ( 0 , 50 , 1000 mg/day ) by a three‐by‐three factorial design using 54 subjects ( age range=40–69 years ) . Serum concentrations of carotenoids , α‐tocopherol , and ascorbic acid  were examined at baseline , and one , two , and threemonth points . Both serum β‐carotene and ascorbic acid were significantly higher in high‐dose groups than in each placebo group during the supplementation . The serum β‐carotene increased gradually ( 597–830 % increase ) during the study , whereas the serum ascorbic acid reached nearly a steady‐state at the one‐month point and remained stable thereafter ( 88–95 % increase ) . No statistically significant interaction between β‐carotene and vitamin C supplementations was observed either for serum β‐carotene or for serum ascorbic acid . Among carotenoids and α‐tocopherol examined , serum lycopene in the high‐dose β‐carotene group was significantly higher than in the placebo group at all points . No unfavorable change in carotenoids and α‐tocopherol was observed in any group RATIONALE Restoration of vitamin D sufficiency may reduce asthma exacerbations , events that are often associated with respiratory tract infections and cold symptoms . OBJECTIVES To determine whether vitamin D supplementation reduces cold symptom occurrence and severity in adults with mild to moderate asthma and vitamin D insufficiency . METHODS Colds were assessed in the AsthmaNet VIDA ( Vitamin D Add-on Therapy Enhances Corticosteroid Responsiveness ) trial , in which 408 adult patients were r and omized to receive placebo or cholecalciferol ( 100,000 IU load plus 4,000 IU/d ) for 28 weeks as add-on therapy . The primary outcome was cold symptom severity , which was assessed using daily scores on the 21-item Wisconsin Upper Respiratory Symptom Survey . MEASUREMENTS AND MAIN RESULTS A total of 203 participants experienced at least one cold .  Despite achieving 25-hydroxyvitamin D levels of 41.9 ng/ml ( 95 % confidence interval [ CI ] , 40.1 - 43.7 ng/ml ) by 12 weeks , vitamin D supplementation had no effect on the primary outcome : the average peak WURSS-21 scores ( 62.0 [ 95 % CI , 55.1 - 68.9 ; placebo ] and 58.7 [ 95 % CI , 52.4 - 65.0 ; vitamin D ] ; P = 0.39 ) . The rate of colds did not differ between groups ( rate ratio [ RR ] , 1.2 ; 95 % CI , 0.9 - 1.5 ) ; however , among African Americans , those receiving vitamin D versus placebo had an increased rate of colds ( RR , 1.7 ; 95 % CI , 1.1 - 2.7 ; P = 0.02 ) . This was also observed in a responder analysis of all subjects achieving vitamin D sufficiency , regardless of treatment assignment ( RR , 1.4 ; 95 % CI , 1.1 - 1.7 ; P = 0.009 ) . CONCLUSIONS Our findings in patients with mild to moderate asthma undergoing an inhaled corticosteroid dose reduction do not support the use of vitamin D supplementation for the purpose of reducing cold severity or frequency 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 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 Background Vitamin C or ascorbic acid is a hydro-soluble lactone ( synthesized from glucose ) essential to human body and available from diet . Despite its broad availability in fruits and vegetables , in many developing countries the incidence of clinical symptoms due to the vitamin deficiency is still very high . Also , pregnant women in the developing countries are frequently hospitalized for several preventable reasons such as anemia in pregnancy , mostly iron-deficient anemia ( IDA ) and the upper/lower respiratory tract infections ( RTI ) . The aim of the study was to investigate , in a Ug and an rural pregnant women cohort , the preventive effects of vitamin C supplementation on hospital admission . Methods 384 pregnant women met the inclusion criteria and were r and omly assigned to receive either 400 mg of vitamin C daily ( 187 ) or not ( 197 ) in addition to their st and ard antenatal vitamins until delivery . The primary outcome measure of this study was to assess the prevention of hospitalization during pregnancy in the group of women supplemented with vitamin C compared to the controls . Fisher‘s exact test was employed in this assessment . Results 42.2 % women in the vitamin C group and 27.9 % in the control group were not hospitalized during pregnancy ; this difference was found statistically significant . Conclusion The results of this study suggest including vitamin C in the guidelines of multivitamin prevention for pregnant women , especially in developing countries where seasonal availability of fruits and vegetables could result in adverse clinical outcomes 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 One hundred sixty-eight volunteers were r and omized to receive a placebo or a vitamin C supplement , two tablets daily , over a 60-day 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 . Compared with the placebo group , the active-treatment group had significantly fewer colds ( 37 vs 50 , P<.05 ) , fewer days challenged virally ( 85 vs 178 ) , and a significantly shorter duration of severe symptoms ( 1.8 vs 3.1 days , P<.03 ) . Consequently , volunteers in the active group were less likely to get a cold and recovered faster if infected . Few side effects occurred with the active treatment , and volunteers reported greatly increased satisfaction with the study supplement compared with any previous form of vitamin C. This well-tolerated vitamin C supplement may prevent the common cold and shorten the duration of symptoms . Volunteers were generally impressed by the protection afforded them during the winter months and the general acceptability of the study medication Osteoporosis is a major public health issue leading to significant morbidity , loss of independence and excess loss of life . It has been estimated that 13 to 17 million postmenopausal women have low bone mass or osteoporosis ( 1 , 2 ) . This is associated with almost 1.5 million fractures annually , including 300,000 hip fractures ( 2 , 3 ) . A review of the evidence by Cumming in 1990 ( 4 ) and subsequently published r and omized clinical trials have shown that calcium and /or vitamin D supplements may play a role in the prevention and treatment of osteoporosis by slowing the rates of bone loss in postmenopausal and elderly women ( 5–9 ) . However , there are a limited number of calcium and /or vitamin D trials ( 10–13 ) and observational studies [ review of evidence by Cumming and Nevitt ( 14 ) and Kanis ( 15 ) ] , to support a role for calcium and vitamin D supplementation in the reduction of hip and other fractures . It has also been suggested that calcium and vitamin D supplementation may play a role in the reduction of colorectal cancer incidence ( 16–21 ) . To address these major health concerns of postmenopausal women , the Calcium-Vitamin D ( CaD ) trial of the Women ’s Health Initiative ( WHI ) was design ed to test the primary hypothesis that women who are r and omized to receive calcium and vitamin D supplementation will have a lower risk of hip fracture and secondarily , a lower risk of all fractures and colorectal cancer than women receiving corresponding placebo . The objective of this paper is 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 Introduction Maternal vitamin D status in pregnancy has been linked to many health outcomes in mother and offspring . A wealth of observational studies have reported on both obstetric outcomes and complications , including pre-eclampsia , gestational diabetes , mode and timing of delivery . Many foetal and childhood outcomes are also linked to vitamin D status , including measures of foetal size , body composition and skeletal mineralization , in addition to later childhood outcomes , such as asthma . Sources of data Synthesis of systematic and narrative review s. Areas of agreement and controversy The findings are generally inconsistent in most areas , and , at present , there is a lack of data from high- quality intervention studies to confirm a causal role for vitamin D in these outcomes . In most areas , the evidence tends towards maternal vitamin D being of overall benefit , but often does not reach statistical significance in meta-analyses . Growing points and areas timely for developing research The most conclusive evidence is in the role of maternal vitamin D supplementation in the prevention of neonatal hypocalcaemia ; as a consequence the UK department of health recommends that pregnant women take 400 IU vitamin D daily . High- quality r and omized placebo-controlled trials , such as the UK-based MAVIDOS trial , will inform the potential efficacy and safety of vitamin D supplementation in pregnancy across a variety of outcomes 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 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 A potential role for oxidative stress in the pathophysiology of pre-eclampsia was first proposed by Stark in 1993 . Synthesis of free radicals by a dysfunctional placenta , and possibly by maternal leucocytes and endothelium , seems to play a central role in this association . Free radicals , through oxidative damage of biomolecules and lipid peroxidation , can initiate maternal vascular endothelial dysfunction and leucocyte activation . A comprehensive review of the role of oxidative stress in pre-eclampsia has been recently published . Antioxidants such as vitamin C and vitamin E have been proposed as potential therapeutic or prophylactic treatment for pre-eclampsia .  This suggestion was supported by the observation that women with pre-eclampsia have lower plasma vitamin C concentrations . Both in vitro and in vivo studies suggest that there is an interaction between vitamin C and vitamin E , with vitamin C possibly exerting a ‘ redox ’ recycling effect on oxidised vitamin E within lipoproteins and membranes . The vitamin C to E ratio may be of central importance in protecting against the damaging effects of reactive oxygen species . To date , three placebo-controlled trials have assessed the effect of vitamins C and E on  pre-eclampsia .  Although no benefits were found when supplementation was given to women with diagnosed pre-eclampsia , a combination of 1 g/day of vitamin C and 400 IU/day of vitamin E given as prophylaxis to high risk women demonstrated a reduction in the risk of pre-eclampsia from 17 % in the control group to 8 % in the active treatment group . In this same double-masked r and omised controlled trial , women receiving vitamins C and E showed a reduction in biological markers of oxidative stress . Since this report , a number of multicentre r and omised clinical trials have been initiated both in low risk and in high risk population s , with the goal of testing the hypothesis that antioxidants reduce the incidence of pre-eclampsia ( Table 1 ) . In the UK , a multicentre trial is currently recruiting pregnant women with diabetes . The NIH has funded two antioxidant trials , one that is under way in Brazil and the second that is being conducted among nulliparous women in the NICHD Maternal Fetal Medicine Network . The International Trial of Antioxidants for the Prevention of Preeclampsia ( INTAPP ) , funded by the Canadian Institutes of Health Research , is enrolling nulliparas without additional risk factors ( Stratum I ) and multiparas and nulliparas with clinical risk factors for gestational hypertension ( Stratum II ) . Collectively , these trials should provide an answer to the question of the role of antioxidants in the prevention of pre-eclampsia and its related disorders . Recently , a meta- analysis of 19 clinical trials of  vitamin E  , for the most part secondary prevention trials , conducted in elderly population s at increased risk for a number of diseases ranging from lung or gastrointestinal cancer to cardiovascular disease , Alzheimer ’s disease or cataract , was published in the Annals of Internal Medicine . The authors of the meta- analysis concluded that high doses of vitamin E may be associated with an increased risk of all-cause mortality . What are the implication s of this meta- analysis for the ongoing pre-eclampsia prevention trials ? It is the responsibility of the Principal Investigators , the Steering Committees and Data Safety Monitoring Committees ( DSMC ) of ongoing clinical trials to take into account information generated from studies that arise in the course of their trial . They must assess the quality of the new evidence and determine how this information influences the balance of risks to benefits of the ongoing trials . In the case of the Canadian trial , both the DSMC and the hospital Ethics Committee have review ed the information and made their recommendations to the trial Steering Committee . The following is our evaluation of the quality of the evidence of the meta- analysis by Miller et al. , and its implication s for ongoing clinical trials of antioxidants in the prevention of pre-eclampsia 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 OBJECTIVE A r and omized , double-blind , placebo-controlled intervention study was carried out in order to investigate whether consumption of a dietary supplement containing probiotic bacteria plus vitamins and minerals over a period of at least three months in winter/spring affects the duration , frequency , and severity of symptoms of naturally acquired common cold infections as well as cellular immune parameters . METHODS 477 healthy men and women ( aged 36 + /- 13 , mean + /- SD ) who had not been vaccinated against influenza were r and omly assigned to a group who received daily the probiotic multivitamin and mineral supplement ( verum ) or a placebo , for three ( n = 239 ) or for 5.5 months ( n = 238 ) . Cellular immune response was determined in 60 participants per study group by flow cytometry before and after 14 days of supplementation . RESULTS The incidence of respiratory tract infections regarded as being virally induced was 13.6 % lower in the verum group compared to the placebo group ( p = 0.07 ) . During respiratory tract infection episodes , the subjects recorded common cold and influenza-like symptoms daily . All symptoms were reduced in the verum group . We found a relative reduction of 19 % in the total symptom score ( p = 0.12 ) , 25 % in influenza symptoms ( p = 0.09 ) , and 54 % in the number of days with fever ( p = 0.03 ) . The duration of these infections was not affected . Leukocytes , lymphocytes , in particular T-lymphocytes including CD4 + and CD8 + cells , as well as monocytes were significantly higher increased in the verum group , during the first 14 days of supplementation compared to placebo . CONCLUSION These data indicate that the intake of a dietary supplement containing probiotic bacteria plus vitamins and minerals during a period of at least three months in winter/spring may reduce the incidence and the severity of symptoms in common cold infections in otherwise healthy adults . This may be due to stimulated cellular immunity 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 CONTEXT Respiratory tract infections are prevalent in elderly individuals , result ing in increased morbidity , mortality , and use of health care services . Vitamin E supplementation has been shown to improve immune response in elderly persons . However , the clinical importance of these findings has not been determined . OBJECTIVE To determine the effect of 1 year of vitamin E supplementation on respiratory tract infections in elderly nursing home residents . DESIGN , SETTING , AND PARTICIPANTS A r and omized , double-blind , placebo-controlled trial was conducted from April 1998 to August 2001 at 33 long-term care facilities in the Boston , Mass , area . A total of 617 persons aged at least 65 years and who met the study 's eligibility criteria were enrolled ; 451 ( 73 % ) completed the study . INTERVENTION Vitamin E ( 200 IU ) or placebo capsule administered daily ; all participants received a capsule containing half the recommended daily allowance of essential vitamins and minerals . MAIN OUTCOME MEASURES Incidence of respiratory tract infections , number of persons and number of days with respiratory tract infections ( upper and lower ) , and number of new antibiotic prescriptions for respiratory tract infections among all participants r and omized and those who completed the study . RESULTS Vitamin E had no significant effect on incidence or number of days with infection for all , upper , or lower respiratory tract infections . However , fewer participants receiving vitamin E acquired 1 or more respiratory tract infections ( 60 % vs 68 % ; risk ratio [ RR ] , 0.88 ; 95 % confidence interval [ CI ] , 0.76 - 1.00 ; P = .048 for all participants ; and 65 % vs 74 % ; RR , 0.88 ; 95 % CI , 0.75 - 0.99 ; P = .04 for completing participants ) , or upper respiratory tract infections ( 44 % vs 52 % ; RR , 0.84 ; 95 % CI , 0.69 - 1.00 ; P = .05 for all participants ; and 50 % vs 62 % ; RR , 0.81 ; 95 % CI , 0.66 - 0.96 ; P = .01 for completing participants ) . When common colds were analyzed in a post hoc subgroup analysis , the vitamin E group had a lower incidence of common cold ( 0.67 vs 0.81 per person-year ; RR , 0.83 ; 95 % CI , 0.68 - 1.01 ; P = .06 for all participants ; and 0.66 vs 0.83 per person-year ; RR , 0.80 ; 95 % CI , 0.64 - 0.98 ; P = .04 for completing participants ) and fewer participants in the vitamin E group acquired 1 or more colds ( 40 % vs 48 % ; RR , 0.83 ; 95 % CI , 0.67 - 1.00 ; P = .05 for all participants ; and 46 % vs 57 % ; RR , 0.80 ; 95 % CI , 0.64 - 0.96 ; P = .02 for completing participants ) . Vitamin E had no significant effect on antibiotic use . CONCLUSIONS Supplementation with 200 IU per day of vitamin E did not have a statistically significant effect on lower respiratory tract infections in elderly nursing home residents . However , we observed a protective effect of vitamin E supplementation on upper respiratory tract infections , particularly the common cold , that merits further investigation Summary of the Recommendations The U.S. Preventive Services Task Force ( USPSTF ) concludes that the evidence is insufficient to recommend for or against the use of supplements of vitamins A , C , or E ; multivitamins with folic acid ; or antioxidant combinations for the prevention of cancer or cardiovascular disease . This is a grade I recommendation . ( See Appendix Table 1 for a description of the USPSTF classification of recommendations . ) The USPSTF found poor evidence to determine whether supplementation with these vitamins reduces the risk for cardiovascular disease or cancer . ( See Appendix Table 2 for a description of the USPSTF classification of levels of evidence . ) The available evidence from r and omized trials is either inadequate or conflicting , and the influence of confounding variables on observed outcomes in observational studies can not be determined . As a result , the USPSTF could not determine the balance of benefits and harms of routine use of supplements of vitamins A , C , or E ; multivitamins with folic acid ; or antioxidant combinations for the prevention of cancer or cardiovascular disease . The USPSTF recommends against the use of beta-carotene supplements , either alone or in combination , for the prevention of cancer or cardiovascular disease . This is a grade D recommendation . The USPSTF found good evidence that -carotene supplementation provides no benefit in the prevention of cancer or cardiovascular disease in middle-aged and older adults . In two trials restricted to heavy smokers , -carotene supplementation was associated with higher incidence of lung cancer and higher all-cause mortality . The USPSTF concludes that -carotene supplements are unlikely to provide important benefits and might cause harm in some groups . Clinical Considerations The USPSTF did not review evidence regarding vitamin supplementation for patients with known or potential nutritional deficiencies , including pregnant and lactating women , children , elderly persons , and people with chronic illnesses .  Dietary supplements may be appropriate for people whose diet does not provide the recommended dietary intake of specific vitamins . Individuals may wish to consult a health care provider to discuss whether dietary supplements are appropriate . With the exception of vitamins for which there is compelling evidence of net harm ( for example , beta-carotene supplementation in smokers ) , there is little reason to discourage people from taking vitamin supplements . Patients should be reminded that taking vitamins does not replace the need to eat a healthy diet . All patients should receive information about the benefits of a diet high in fruits and vegetables , as well as information on other foods and nutrients that should be emphasized or avoided in their diet ( see the 2002 USPSTF recommendations on counseling to promote a healthy diet [ 1 ] ) . Patients who choose to take vitamins  should be encouraged to adhere to the dosages recommended in the Dietary Reference Intakes of the Institute of Medicine . Some vitamins , such as A and D , may be harmful in higher doses ; therefore , doses greatly exceeding the Recommended Dietary Allowance or Adequate Intake should be taken with care while considering whether potential harms outweigh potential benefits . Vitamins and minerals sold in the United States are classified as dietary supplements , and there is a degree of quality control over content if they have a U.S. Pharmacopeia seal ( 2 ) . Nevertheless , imprecision in the content and concentration of ingredients could pose a theoretical risk not reflected in clinical trials using calibrated compounds . The adverse effects of beta-carotene on smokers have been observed primarily in those taking large supplemental doses . There is no evidence to suggest that beta-carotene is harmful to smokers at levels occurring naturally in foods . The USPSTF did not review evidence supporting folic acid supplementation among pregnant women to reduce neural tube defects . In 1996 , the USPSTF recommended folic acid for all women who are planning , or capable of , pregnancy ( see the 1996 USPSTF chapter on screening for neural tube defects [ 3 ] ) . Clinicians and patients should discuss the possible need for vitamin supplementation when taking certain medications ( for example , folic acid supplementation for patients taking methotrexate ) . Scientific Evidence The USPSTF review s ( 4 - 6 ) focused on the quality of the evidence regarding the effect of routine supplementation with certain vitamins on primary prevention of cancer and cardiovascular disease . These review s were undertaken because of the growing epidemiologic evidence that dietary factors may play a role in the etiology of these diseases ( 7 - 9 ) . The review s focused on prospect i ve trials of vitamin supplementation and observational studies of associations between the use of specific supplements and the risk for cancer or cardiovascular disease . The value of vitamins naturally occurring in food , the use of vitamin supplements for the prevention of other conditions ( for example , neural tube defects ) , and the use of vitamin supplements for the secondary prevention of complications in patients with existing disease were outside the scope of these review s. Vitamin A No prospect i ve trials have examined the effect of vitamin A supplements alone on the risk for cancer . Observational studies provide no evidence that such supplements prevent cancer in men . In women , observational studies have reported a statistically significant inverse association between use of vitamin A supplements and risk for colon and breast cancer ( 10 , 11 ) . Despite efforts to adjust for confounding variables , the observational , nonr and om design of these studies makes it difficult to assess the extent to which the reduced cancer risk is attributable to vitamin A or to other characteristics of women who take vitamin A supplements .  No evidence from prospect i ve trials is available regarding the benefits of vitamin A alone in preventing cardiovascular disease . One good- quality cohort study found no effect of vitamin A supplementation in reducing cardiovascular disease mortality ( 12 ) . Vitamin C No primary prevention trial of the effect of vitamin C supplementation alone on cancer or cardiovascular disease has been reported . Observational studies have generally shown no statistically significant associations between use of vitamin C supplements and risk for cancer of the breast , prostate , colon , or lung ( 12 - 14 ) . The observational cohort studies examining the effects of vitamin C on cardiovascular disease have produced inconsistent results ( 12 , 15 , 16 ) . Vitamin E Only a few trials have examined the effects of vitamin E on the primary prevention of cancer or cardiovascular disease . A r and omized , controlled trial ( RCT ) involving Finnish male smokers found that vitamin E supplementation is not protective against lung cancer but may have a beneficial impact on prostate cancer ( 14 ) . Because prostate cancer was not a primary end point of the trial and the trial had other limitations , further evidence is needed to confirm this finding . Observational studies have shown no statistically significant association between use of vitamin E supplements and risk for prostate , lung , or breast cancer ( 5 ) . One study suggested that vitamin E protects against colon cancer , but the influence of confounding variables can not be fully excluded ( 17 ) . Among primary prevention trials , two good- quality trials ( 14 , 18 ) and one fair- quality trial ( 19 ) found no statistically significant benefit of vitamin E supplementation in preventing cardiovascular disease ( 20 ) . Only one of seven trials of vitamin E supplementation for secondary prevention demonstrated a statistically significant reduction in cardiac events ( 4 ) . Some prospect i ve cohort studies have suggested a significant benefit , but the results are mixed and the influence of confounding variables can not be excluded ( 4 ) . -Carotene A consistent body of evidence from clinical trials suggests that beta-carotene supplementation does not decrease the risk for lung , prostate , colon , breast , or nonmelanoma skin cancer ( 14 , 21 - 25 ) . -Carotene supplements were associated with an increased risk for lung cancer among smokers , especially heavy smokers , in two RCTs ( 14 , 25 ) . Results from four RCTs demonstrated no reduced risk for cardiovascular events or death after beta-carotene supplementation ( 14 , 21 , 22 , 26 - 28 ) . Antioxidant Vitamin Combinations Studies of the effects of antioxidant vitamin combinations to prevent cancer have yielded mixed results . A recent RCT reported no statistically significant effect of daily supplementation with a combination of antioxidants : vitamin E , vitamin C , and beta-carotene ( 29 ) . Some studies have suggested an adverse effect of antioxidant combinations on cancer , but the results may have been confounded by the inclusion of beta-carotene ( 5 ) . Some observational studies of antioxidant vitamin combinations have suggested a benefit in preventing cardiovascular disease ( 13 , 30 , 31 ) , but other studies , including well- design ed RCTs , have shown no benefit ( 29 , 32 , 33 ) . One secondary prevention trial showed an increase in all-cause mortality among women taking antioxidant supplements  ( 34 ) . Multiple Vitamin Combinations The incremental benefit of taking supplemental doses of folic acid and B vitamins has been examined by comparing the outcomes of observational studies while controlling for the total intake of antioxidant vitamin supplements ( 35 ) . In these analyses , folic acid supplementation was associated with significantly decreased risk for colon cancer , but the protective effect requires confirmation in prospect i ve trials . There is conflicting evidence regarding the use of multivitamins and the risk for cardiovascular disease . Among cohort studies , one good- quality study reported a statistically significant reduction in coronary events ( 36 ) , two good- quality studies reported no statistically significant effect on mortality ( 16 , 37 ) , and one OBJECTIVE We have previously reported a reduced incidence of preeclampsia in women who were at risk and were taking vitamin C ( 1000 mg/d ) and vitamin E ( 400 IU/d ) supplements . In this study , we determined whether supplementation in the same cohort was associated with an improvement in indices of placental dysfunction and oxidative stress toward values determined in women who were at low risk of preeclampsia . STUDY DESIGN Seventy-nine women who were at high risk and who were taking vitamin supplements and 81 who were taking placebos were compared with 32 women who were at low risk and who were not taking supplements who were studied simultaneously . RESULTS Indices of oxidative stress and placental function were abnormal in the placebo group . When the placebo group was compared with the women who were at low risk , ascorbic acid , plasminogen activator inhibitor-2 , and placenta growth factor concentrations were decreased ; and 8-epi-prostagl and in F(2alpha),leptin , and the plasminogen activator inhibitor-1/-2 ratio were increased . In the group that received vitamin supplements , ascorbic acid , 8-epi-prostagl and in F(2alpha ) , leptin , and plasminogen activator inhibitor-1/-2 values were similar to women who were at low risk . CONCLUSION Antioxidant supplementation in women who were at risk of preeclampsia was associated with improvement in biochemical indices of the disease 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 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
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 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 ?