Cara McGuinness, Jessica Brown, Kiran Kazmi, Aliza Ginzberg, Khalil Hanif

Vitamin Supplements and Cold Prevention

 

Scenario: It’s winter and you’re working in a family practice office.  Many patients are coming in with runny noses and general malaise.  Brenda, a 35-year-old working mother comes in for a checkup and says, “I’m so busy between work and home that I definitely don’t have time to get sick!  Can those zinc or vitamin C pills I hear about prevent colds?”

 

Clinical Question:

Do zinc or vitamin C supplementation pills prevent and/or treat the common cold?

 

PICO Question:

Can zinc or vitamin C pills prevent and/or treat the common cold in adult females.

 

P: adult, female

I: zinc and/or vitamin C supplement

C: no intake of zinc and/or vitamin C (vitamin supplements)

O: cold prevention, symptom relief, decreased cold duration, URI prevention

 

Search Strategy:

Searched Terms: ‘vitamin c cold prevention’; ‘zinc cold prevention’; zinc cold treatment, ‘vitamin C cold treatment’; ‘URI prevention’; ‘URI treatment’

Database and Articles Returned:

PubMed (via ‘best match’) filter: 201→ 3 articles chosen

Cochrane → Review → 84 → 1 article chosen

 

Filters: systematic review AND meta-analysis→ 37 results  (on PubMed) → 1 article chosen

 

Selection Methods (what criteria determined which articles to include in this CAT):

→ See grid below

Adult pt supplementing with Vitamin C

Adult pt supplementing with Zinc

Compared to no intervention / placebo

Common Cold prevention

 

P	I	C	O
adult	Zinc supplement	Placebo	Cold prevention
female	Vitamin C supplement	No intervention	Symptom relief
Middle aged			Decreased duration
			URI prevention

 

 

 

 

 

Articles Chosen for Inclusion:

1. Complementary and alternative medicine for prevention and treatment of the common cold.

Nahas R, Balla A.

Can Fam Physician. 2011 Jan;57(1):31-6. Review.

PMID: 21322286

Abstract

OBJECTIVE:

To review the evidence supporting complementary and alternative medicine approaches to treatment and prevention of the common cold in adults.

QUALITY OF EVIDENCE:

MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews were searched from January 1966 to September 2009 combining the key words common cold or influenza with echinacea, garlic, ginseng, probiotics, vitamin C, and zinc. Clinical trials and prospective studies were included.

MAIN MESSAGE:

For prevention, vitamin C demonstrated benefit in a large meta-analysis, with possibly increased benefit in patients subjected to cold stress. There is inconsistent evidence for Asian ginseng (Panax ginseng) and North American ginseng (Panax quinquefolius). Allicin was highly effective in 1 small trial. For treatment, Echinacea purpurea is the most consistently useful variety; it was effective in 5 of 6 trials. Zinc lozenges were effective in 5 of 9 trials, likely owing to dose and formulation issues. Overall, the evidence suggests no benefit from probiotics for prevention or treatment of the common cold.

CONCLUSION:

Vitamin C can be recommended to Canadian patients for prevention of the common cold. There is moderate evidence supporting the use of Echinacea purpurea and zinc lozenges for treatment. Ginseng and allicin warrant further research.

 

2. Effect of vitamin C on common cold: randomized controlled trial.

Sasazuki S, Sasaki S, Tsubono Y, Okubo S, Hayashi M, Tsugane S.

Eur J Clin Nutr. 2006 Jan;60(1):9-17.

PMID: 16118650

OBJECTIVE:
To investigate the relationship between the common cold and vitamin C supplementation.

DESIGN:
A double-blind, 5-year randomized controlled trial.

SETTING:
A village in Akita prefecture, one of the regions in Japan with the highest mortality from gastric cancer.

SUBJECTS:
Participants in annual screening programs for circulatory diseases conducted under the National Health and Welfare Services Law for the Aged, and diagnosed as having atrophic gastritis. Of the 439 eligible subjects, 144 and 161 were assigned to receive 50 or 500 mg of vitamin C, respectively, after protocol amendment. During the supplementation phase, 61 dropped out, and 244 completed the trial.

INTERVENTION:
Daily vitamin C supplementation of 50 mg (low-dose group) or 500 mg (high-dose group).

RESULTS:
Total number of common colds (per 1000 person-months) was 21.3 and 17.1 for the low- and high-dose groups, respectively. After adjustment for several factors, the relative risks (95% confidence interval (CI)) of suffering from a common cold three or more times during the survey period was 0.34 (0.12-0.97) for the high-dose group. No apparent reduction was seen for the severity and duration of the common cold.

CONCLUSION:
A randomized, controlled 5-year trial suggests that vitamin C supplementation significantly reduces the frequency of the common cold but had no apparent effect on the duration or severity of the common cold. However, considering several limitations due to protocol amendment, the findings should be interpreted with caution.

 

3. A combination of high-dose vitamin C plus zinc for the common cold.

Maggini S, Beveridge S, Suter M.

J Int Med Res. 2012;40(1):28-42. Review.

PMID:22429343

Background: Vitamin C and zinc play important roles in nutrition, immune defence and maintenance of health. Intake of both is often inadequate, even in affluent populations. The common cold continues to place a great burden on society in terms of suffering and economic loss.

Methods:  After an overview of the literature on the effects of the separate administration of either vitamin C or zinc against the common cold, this article presents data from two preliminary, double-blind, randomized, placebo-controlled trials, conducted with a combination of 1000 mg vitamin C plus 10 mg zinc in patients with the common cold.

 

Results: In both studies, a nonsignificant reduction of rhinorrhoea duration (range 9 – 27%) was seen. In pooled analyses of both studies (n = 94), vitamin C plus zinc was significantly more efficient than placebo at reducing rhinorrhoea over 5 days of treatment. Furthermore, symptom relief was quicker and the product was well tolerated.

 

Conclusion: In view of the burden associated with the common cold, supplementation with vitamin C plus zinc may represent an efficacious measure, with a good safety profile, against this infectious viral disease

 

4. Hemilä H, Chalker E. Vitamin C for preventing and treating the common cold. Cochrane Database of Systematic Reviews 2013, Issue 1. Art. No.: CD000980. DOI:10.1002/14651858.CD000980.pub4.

 

Background: Vitamin C (ascorbic acid) for preventing and treating the common cold has been a subject of controversy for 70 years.

Objectives: To find out whether vitamin C reduces the incidence, the duration or severity of the common cold when used either as a continuous regular supplementation every day or as a therapy at the onset of cold symptoms.

Search methods: We searched CENTRAL 2012, Issue 11, MEDLINE (1966 to November week 3, 2012), EMBASE (1990 to November 2012), CINAHL (January 2010 to November 2012), LILACS (January 2010 to November 2012) and Web of Science (January 2010 to November 2012). We also searched the U.S. National Institutes of Health trials register and WHO ICTRP on 29 November 2012.

Selection criteria: We excluded trials which used less than 0.2 g per day of vitamin C and trials without a placebo comparison. We restricted our review to placebo-controlled trials.

Data collection and analysis: Two review authors independently extracted data. We assessed ‘incidence’ of colds during regular supplementation as the proportion of participants experiencing one or more colds during the study period. ‘Duration’ was the mean number of days of illness of cold episodes.

Main results: Twenty-nine trial comparisons involving 11,306 participants contributed to the meta-analysis on the risk ratio (RR) of developing a cold whilst taking vitamin C regularly over the study period. In the general community trials involving 10,708 participants, the pooled RR was 0.97 (95% confidence interval (CI) 0.94 to 1.00). Five trials involving a total of 598 marathon runners, skiers and soldiers on subarctic exercises yielded a pooled RR of 0.48 (95% CI 0.35 to 0.64). Thirty-one comparisons examined the effect of regular vitamin C on common cold duration (9745 episodes). In adults the duration of colds was reduced by 8% (3% to 12%) and in children by 14% (7% to 21%). In children, 1 to 2 g/day vitamin C shortened colds by 18%. The severity of colds was also reduced by regular vitamin C administration. Seven comparisons examined the effect of therapeutic vitamin C (3249 episodes). No consistent effect of vitamin C was seen on the duration or severity of colds in the therapeutic trials. The majority of included trials were randomised, double-blind trials. The exclusion of trials that were either not randomised or not double-blind had no effect on the conclusions.

Authors’ conclusions: The failure of vitamin C supplementation to reduce the incidence of colds in the general population indicates that routine vitamin C supplementation is not justified, yet vitamin C may be useful for people exposed to brief periods of severe physical exercise. Regular supplementation trials have shown that vitamin C reduces the duration of colds, but this was not replicated in the few therapeutic trials that have been carried out. Nevertheless, given the consistent effect of vitamin C on the duration and severity of colds in the regular supplementation studies, and the low cost and safety, it may be worthwhile for common cold patients to test on an individual basis whether therapeutic vitamin C is beneficial for them. Further therapeutic RCTs are warranted.

 

 

5. Intake of vitamin C and zinc and risk of common cold: a cohort study.

Takkouche B, Regueira-Méndez C, García-Closas R, Figueiras A, Gestal-Otero JJ.

Epidemiology. 2002 Jan;13(1):38-44.

PMID: 11805584

 

Abstract: To examine whether intake of vitamin C and zinc is associated with a decrease in the risk of a common cold, we analyzed data from a cohort study carried out in a population of 4,272 faculty and staff from five Spanish universities. Participants were 21–65 years of age, were full-time workers at those universities, and did not have antecedents of asthma or chronic obstructive pulmonary disease. Daily intake of vitamin C and zinc was assessed at baseline by means of a food frequency questionnaire of which the validity and reproducibility were determined in a sample of the population. Subjects were traced for 1 year to detect episodes of common cold, the diagnosis of which was based on symptoms and was validated by additional clinical signs. We detected 1,667 cases of common cold in 79,240 person-weeks of follow-up. Intake of vitamin C and zinc was not related to the occurrence of common cold. Compared with the first quartile of intake, women in the fourth quartile of vitamin C intake showed an adjusted incidence rate ratio of 1.0 (95% CI = 0.7–1.3), and for zinc intake this figure was 1.1 (95% CI = 0.8–1.5). The incidence rate ratios for men in the fourth quartile were 1.1 (95% CI = 0.8–1.4) for vitamin C and 1.3 (95% CI = 0.9–1.8) for zinc.

 

 

Summary of the Evidence:

Author (Date)	Level of Evidence	Sample/Setting (# of subjects/ studies, cohort definition etc. )	Outcome(s) studied	Key Findings	Limitations and Biases
Nahas R, Balla A (2011)	Systematic Review	Searched MEDLINE, EMBASE and Cochrane Database, looking for studies (they also included clinical trials and prospective studies) from January 1966 to September 2009. They used the search words: common cold, influenza along with echinacea, garlic, ginseng, probiotics, vitamin C, and zinc. For our purposes we focused on the portions of this review that involved Vitamin C and Zinc.   Vitamin C Prevention: –Review found 30 prevention trials that included 11,450 subjects. –a subset of these studies (6 trials) of 642 subjects under severe stress   Vitamin C Treatment: –Cochrane systematic review of 7 treatment trails that analyzed 3294 episodes of the common cold.   Zinc Prevention: –No trials found   Zinc Treatment: — analyzed in 13 trials. In 4 of the trials a nasal spray was compared w/ placebo. –An analysis was done of the remaining 9 trials that involved Zinc lozenges.	Effects of Vitamin C supplement and/or Zinc supplements on the prevention and treatment of the common cold.	Vitamin C and Prevention: found that there was a slight decrease in the number of colds with the use of vitamin C (95% confidence interval, 0.92-1.0, OR=.96) and there was no decrease in cold severity. Symptom duration decrease by 8% in the trials that used more than 1g of Vitamin C daily in adults. They then went on to assume that the average cold lasts 7-10 days and calculated that using Vitamin C supplements results in a 1.5-2.0 days decrease in cold length, which they claimed to be clinically relevant. Analysis of 6 of the trials found that vitamin C had a higher prevention in those adults under high stress taking a dose of 200-2000 mg daily (they had ½ as many colds compared to the placebo; 95% confidence interval 0.38-0.66).   Vitamin C and Treatment: only one of the 7 trials studied found that a dose of 8g of vitamin C at the start of cold symptoms results in shorter colds compared to those who took a 4g dose (46% v 39%, P=.046). While the remaining studies found no benefit of vitamin C for the prevention of a cold, even using similar dosing.   Zinc and Treatment: Nasal sprays→ only 2 of the 13 studies found that a zinc spray compared to a placebo reduced the duration and severity of the cold.   Zinc and Tx:  Lozenges→ in 5 of the 9 trials it was found that there was a reduction in symptom duration and severity. ⅘ studies used high dose zinc (13-23 mg/lozenge q2 hours) lead to a 1.3-6.9 day decrease in symptoms and severity. Dosage and bioavailability play a role in interpreting the results of this study. Bioavailability and dose could play a role in the variable results that were found in the meta-analysis of  8 RCTS (OR 0.52, 95% CI 0.25-1.2) for symptoms after 7 days.	Limitations: Zinc nasal sprays→  Irritation by the spray did result in a limitation of limit their use and it was found that “they appear to yield lower concentrations in the nasopharynx.” Zinc Lozenges→ results were difficult to interpret because of dosing: ⅘ studies that used high doses of zinc (13-23 mg/lozenge q2 hours) lead to decrease in duration symptoms and severity, while “negative trials using lower doses have been criticized.” The second problem is bioavailability: negative trials were criticized for using formulas that included “citric acid or tartaric acid, sorbitol or mannitol all of which bind to and inactive elemental zinc.” while positive trials used acetate or gluconate which do not bind as tightly to zinc.This limited to the study because there is the possibility of confounding factors determining whether the lozenges were effective or not   Could have been more clear about how the selection criteria. There was no mention in what age/gender/race etc they were looking into. While they did specify when results were relevant to children or adults it would have been beneficial to know what criteria they used.   While the authors provided the CIs in the statistical analysis they did not specify which results were statistically significant but rather told us what they deemed could be “relevant” or “clinically relevant.”
Sasazuki S, Sasaki S, Tsubono Y, Okubo S, Hayashi M, Tsugane S. (2006)	Double-blind randomized control trial	1231 patients screened, 439 eligible subjects (selected from the participants in annual screening programs for circulatory disease under the National Health & Welfare Services Law for the Aged and diagnosed as having atrophic gastritis) → initial participants were selected for the purpose of a broader study that was looking to study effects of beta-carotene supplementation and vitamin C on the incidence of gastric cancer. The study was later repurposed to look at the effects of Vitamin C on the common cold when it was determined that beta-carotene could not be used in a trial setting.  All of the participants in this study thus have atrophic gastritis due to their initial inclusion criteria.  Some participants dropped out (details provided below), there were ultimately 244 individuals that remained in the study.  No new participants were added. 305 selected for participation in a 5 year double-blind, randomized control trial → 144 were assigned to receive 50 mg of vitamin C → 161 were assigned to receive 500 mg of vitamin C   –        61 dropped out –        244 patients completed the trial (61 patients dropped out) **Note: initial study were randomized in a double-blind manner to one of four groups using 2 x 2 factorial design and treated with beta-carotene and vitamin C → when NCI released results from two trials that beta-carotene had no benefit but showed potential harm, the study protocol was amended   N = 244, study participants willing to remain in study → 120 were assigned to receive 50 mg of vitamin C → 124 were assigned to receive 500 mg of vitamin C	Effect of Vitamin C in preventing the common cold.   Vitamin C supplementation significantly reduces the frequency of the common cold → no apparent effect on the duration/severity of the cold → the presence of atrophic gastritis had diminished absorptive properties, likely due to the destruction of the gastric mucosa.  Given the patients were initially recruited for another study, it is understandable that they all have gastritis but makes the results less applicable for the purposes of this study.  With decreased absorption, patients may not receive the same amount of Vitamin C as an individual that did not have atrophic gastritis and thus wouldn’t receive the full benefits of Vitamin C in cold prevention.  This factor is significant as it relates to our patient — if we were not attune to these points, the study could have guided us in a way that may not have been as relevant or significant for our particular patient, especially because she does not have atrophic gastritis.	For majority of the study period, the high-dose group were less likely to report a common cold April-June 1999 →  Incidence of common cold in low-dose group 9.2%  (P = 0.05) → Incidence of common cold in high-dose group 3.2% (P = 0.05) Total Colds Reported during supplementation period (per 1000 person-months) → 21.3 for the low-dose group → 17.1 for the high-dose group   Estimates of Relative Risk were obtained for the common cold with adjustments made for confounding factors → the presence of a common cold three or more times during the RCT, ~ 70% reduction in RR was observed (0.34, 95% CI; 0.12-0.97, P = 0.04) for the high-dose group → the presence of a common cold four or more times during the RCT was only seen ~ 10 times (0.28, 95%, CI: 0.06-1.28, P= 0.10) → NOTE: I attempted to calculate the Absolute Risk to make better sense of this article; however, the numbers the researchers utilized to calculate the Relative Risk were not published/ available to the reader and therefore, was unable to calculate the AR without these data points.   Adjustments include age, sex, BMI, cigarette smoking, alcohol drinking, dietary intake of green/yellow vegetables, other vegetables, fruits and vitamin C. Reported via patient survey.   RCT findings were very similar for the completed group analysis as they were for the intention-to-treat Total Colds Reported during supplementation period (per 1000 person-months) → 21.0 for the low-dose group → 17.5 for the high-dose group   Crude/Adjusted means of duration of the cold (looked at duration of cough, runny nose, sore throat) found: → high-dose group had longer duration colds than those in the low-dose group **only statistically significant finding was the runny nose → NOTE: this is an unexpected finding, but an interesting point that those taking the higher dose vitamin C sample had longer reports of symptoms, which further supports the researchers point, that there was no effect on duration. However, it is important to note that the only statistically significant point is the duration of the runny nose and the other data points are not statistically valid.	Adjusted Protocols: given the updated effects of the beta-carotene, the study’s protocols were adjusted and repurposed for use in determining Vitamin C’s role in preventing the common cold.  This was not the initial intention and the study population may have been different if this had been the initial goal. Small Sample Size: again, the initial purpose of this study changed after the adjusted protocols; however, new participants were not added and there were several that dropped out leading to a small(er) than normal sample size. Lack of definition: the study’s researchers did not clearly define a ‘common cold’ for their participants.  While there was a general guideline, what is a severe cold for one person may not be for the next and that can lead to false reporting of common colds, thus skewing the results and subsequent findings. No control group: The study only tested high-dose and low-dose vitamin C supplementation but did not include a control group (taking a placebo pill) to compare their findings against. Statistical Significance: Was reported differently in different areas and the researcher clearly states the reader should use caution in interpreting results — even though their findings were in line with the largest trials (used as standard, from the 1970s)   It is important to note that the population included in the study indcluded a group of individuals from a region in Japan that reportedly has the highest mortality rate associated with gastric cancer.  However, the authors did not discuss why this chose this population aside from the fact that they were selected following the National Health and Welfare Services Law for the Aged annual health checkup programs.  In doing other research, it seems as though the environmental factors plays a role in the increased likelihood of these individuals acquiring gastric gancer.
Maggini S, Beveridge S, Suter M.	Randomized Cohort Prospective	2 studies were done in France by general practitioners, in which treatment was allocated according to randomization (treatment/placebo was assigned a designated number). A cohort prospective study.Both studies included men and women over the age of 18, who had simple, uncomplicated common cold, and were experiencing rhinorrhea for less than 3 days, rectal temperature was less than 38 degrees Celcius, and informed consent was given. Evaluation of symptoms and global discomfort was tested by time and treatment. Both studies were double-blind, randomized, placebo-controlled pilot, in which patients either received the treatment (1000 mg vitamin C plus 10 mg zinc) or a placebo. Patients were required to evaluate their intensity of usual symptoms of the common cold everyday, as well as discomfort. Common-cold symptoms were evaluated by investigators at days 0 and 6 for study 1, and 0 and 11 for study 2. Adverse effects were also noted. Study1 involved 30 patients with the treatment lasting 5 days. Study 2 involved 64 patients, that were given the treatment for 10 days. Pooled analysis was conducted because both studies were so similar, the sample was combined and data was concluded separately from that analysis.	Study 1: 14 patients had the treatment, 16 had the placebo. Treatment group was found to reduce the mean duration of rhinorrhea by 27% when compared with the placebo. The difference was not statistically significant. Study 2: 32 patients that had treatment, 32 had the placebo. Treatment group experienced a reduced duration of rhinorrhea by 9%, which is not statistically significant, but discomfort due to nasal obstruction and rhinorrhea was significantly lowered by the treatment (p=.05) and (p=04). Pooled Analyses: Rate of definite relief from rhinorrhea was significantly higher in treatment group (P=.03). Relief of treatment was quicker than placebo, began to show benefit at 3 days, (P=.001). Although other symptoms, besides rhinorrhea did not show a difference, significantly great relief was seen in the treatment group of nasal obstruction, sneezing, and eye watering discomfort (p=.02) when compared to the placebo.	Even though a reduction in Rhinorrhea was seen in both studies when using the treatment, the results were still not statistically significant on their own. This might be due to the fact that the study was very small ( less than a 100 people) and it’s duration was short as well. Even though the pooled analysis showed some significance, in terms of relief of rhinorrhea during the first 5 days of treatment, and “less pronounced” discomfort due to nasal obstruction, watery eyes, and sneezing, the article mentions that further investigation needs to take place in order to see significant results.	Limitations:   Very small sample size, less than 100. Very small study, overall less than 2 weeks. Also  the common cold normally subsides itself in a few days as well, so it is very difficult to really assess if there is a true significant difference in the study. There could have been recording bias, where the patient might have thought they were getting better regardless if they got the placebo or treatment.
Hemila H, Chalker E  (2013)	Meta Analysis	This study was conducted by doing a search of CENTRAL, MEDLINE, EMBASE, CINAHL, LILACS, Web of Science, the U.S. NIH trials register, and WHO ICTRP from 1966 to 2012.   Trials which used less than 0.2 g per day of vitamin C or without a placebo comparison were not included. Trials included were randomized and double-blind trials. Exclusion of trials that did meet these requirements had no effect on the conclusions drawn.   The meta-analysis on the risk ratio (RR) of developing a cold while taking vitamin C daily included 29 trial comparisons with a total of 11, 306 participants. This involved two groups. The first group was general community which included 10, 708 participants. The second group included five trials of 598 marathon runners, skiers, and soldiers on subarctic exercises.   The meta-analysis on the effect of regular vitamin C supplementation on common cold duration included 31 comparisons with a total of 9745 cases.   In looking at the effect of vitamin C in treating the common cold, the meta-analysis included 7 comparisons with a total of 3249 cases. These comparisons were between those that received vitamin C therapy with those that did not.	Three outcomes were studied in this meta-analysis:   -The risk of developing a cold while regularly taking vitamin C supplements   -The effect of regularly taking vitamin C on common cold duration/severity   -The effect of regularly taking vitamin C on treating the common cold3	The three key outcomes in this meta-analysis are as follows:   -Vitamin C supplementation had no significant effect in reducing the incidence of common cold in the general population with a pooled RR of 0.97 and 95% Confidence Interval (CI) of 0.94 to 1.00. However, in people exposed to brief periods of intense physical exercise, vitamin C may be useful in reducing incidence of common cold with a pooled RR of 0.48 and a 95% CI of 0.35 to 0.64   -In adults, duration of colds were reduced by 8% (3% to 12%) and in children, and in children 14% (7% to 21%). 1-2 g/day of vitamin C supplementation for children reduced cold duration by 18%. In both adults and children, severity was also reduced by regular vitamin C supplementation.   -No significant consistent effect of  vitamin C supplementation was see on duration or severity in the treatment trials.	-Studies were classified as randomized on many of the study reports included, but only few studies described their actual method of randomizing   -Since there is difference between taste of placebo (sweet) and ascorbic acid in vitamin C supplements, data was only collected on those that reported not being able to distinguish between vitamin C and placebo → No basis to assume that difference in taste could have resulted in substantial bias in the trials   -Most of the identified trials were RCTs and had allocation concealment   -Most of the trials blinded participants, personnel, and outcome assessments   -Many trials did not have drop-outs, but in trials that there were, the number of dropouts was not significantly different between the groups of comparison.   -No basis for speculation that consistency between two outcomes could be explained by selective reporting (publication bias) was found.
Takkouche B, Regueira-Méndez C, García-Closas R, Figueiras A, Gestal-Otero JJ. 2002	Cohort Study with a Validation Substudy	Study includes 4,287 staff members, ages 21-65 years old, from 5 Spanish universities. They were followed for 1 year. They anonymously completed food frequency questionnaires  regarding their diet intake of vitamin c and zinc. Participants filled out a second questionnaire which reported on their medical history, including common cold occurrences for the past year, and other habits. Participants with a history of current common cold, asthma, or COPD were excluded from the study. The participants were divided into  quartiles, based on their intake of vitamin C and zinc:The groups ranged from an intake of Zinc of 4.0mg/day to 9.1mg/day, and the vitamin C groups ranged from 40.3-333.5mg/day.  Throughout the year, participants filled out documents which calculated if they had the common cold – they would rate their severity of 8 particular symptoms such as rhinitis daily (rated from 0- no symptoms, to a 3 – severe), and the researchers collected the data and determined based on a mathematical calculation whether the participant has the cold or not. The researchers compiled the information from the quartiles and compared the incidence of common cold. A validation Substudy was included to assure that the assessment of vitamin c and zinc intake and diagnosis of the common cold was valid and reproducible: 69 participants from the main study were chosen at random and the researchers assessed if the participants had the common cold based on Physical Exam findings and compared it to the rate of diagnosis from the questionnaires. Also, they measured vitamin c and zinc intake over a non consecutive 12 days and compared it to the food frequency assessment of vitamin C and zinc intake.	This study does not prove that a diet rich in vitamin c and zinc is protective against the common cold. However, the treatment of the common cold was not studied; (perhaps these vitamins have a therapeutic effect, but not a preventative effect.)	Vitamin C: intake was not related to incidence of common cold. Throughout the quartiles, the estimated IRR (incidence rate ratio) was 1.0 – 1.1 with a CI of 95%, and not statistically significant (the study reveals confidence intervals for each groups, and they include 0 and 1).   Zinc: intake was not related to common cold incidence. Overall the IRR was about 1.0-1.1, with a 95% CI and like the vitamin C intake, not statistically significant. This study doesn’t provide evidence that a diet rich in vitamin C and zinc has a preventative effect on common cold; however, the intake amounts were less than what supplement/pills equal, so more research is needed to test the effects of supplements.	Attrition Bias: while 22% of the initial participants dropped out, the researchers took that into account. When determining the results they did 2 extremes – first, they presumed that all those that dropped out developed a cold the following week; second, they presumed that none developed the cold. Either way, the overall results were similar. But they don’t reveal those results. Additionally, the researchers simultaneously conducted a validation substudy to confirm that the methods of assessing vitamin c and zinc intake and common cold diagnosis is accurate. However, the article does not reveal the results of the substudy. Perhaps a bias exists here- the results may not be what the researchers wanted so they didn’t expose them.while the IRR for each quartile is published, the actual numbers of participants who had a cold in each group and how many incidences are not revealed.

 

 

 

 

Conclusion(s):

The articles consistently suggest that additional research is needed to determine the true effects of vitamin C and zinc on the common cold.

 

Nahas and Balla’s systematic review should be weighed the most in our decision and recommendation as it surveyed the impact of Vitamin C and Zinc in the treatment and prevention of the common cold.  This systematic review included 50 studies further supporting its effectiveness in guiding decisions.  Vitamin C in high doses (8g) reportedly helps to shorten the duration of the common cold but does not aid in its prevention.  The role of Zinc in preventing the common cold is unknown and further research needs to be done on its impact on the duration of the cold.

While each of the articles were able to provide recommendations for the supplemental use of Vitamin C and Zinc in prevention and treatment of the common cold, there was great inconsistency across the articles reviewed. The Hemila study is a meta-analysis and high on the evidence pyramid; however, it dealt solely with the effect of Vitamin C on prevention and treating the common cold, which lowered its weight when considering recommendations for the patient.

 

The Sasazuki et al. article included patients with atrophic gastritis is not as relevant for the purposes of guiding a patient without atrophic gastritis.  The parallels drawn are not significant because of the absorptive differences of one with and without this illness in addition to the lack of statistically significant findings in the article.

 

The Maggini and Takkouche articles, both cohort studies, fall significantly lower on the evidence pyramid and include small sample sizes and look at supplementation in dietary forms, respectively.  As the goal is to guide the patient in understanding of prevention and treatment of the common cold using these supplements, these were weighed less in the decision making process.

 

It is important to note that articles found using the initial search terms were withdrawn for plagiarism. While these articles were not included in the reviewed articles for the purposes of this assignment; they are still appearing for use in the various searches completed. Finally, many of the articles that appeared in the searches were authored by the same researcher and subsequent articles cited his works as well. The repetitive nature of these findings could lead to potential biases given that the same articles are being used to launch newer studies and a large number of studies are not providing statistically significant results and requiring additional follow up to guide and conclusive evidentiary support.

 

Clinical Bottom Line:

Based on the data, there does not appear to be any statistically significant evidence that indicates taking zinc or vitamin C supplements will prevent the common cold, therefore we would not recommend taking these supplements solely for cold prevention. There were studies that shared clinically relevant results supporting the use of vitamin C in the prevention of the common cold and in its ability to reduce the duration and severity of cold symptoms.  For those purposes, we would recommend our patient use vitamin C supplementation.

 

As providers, we would not deter a patient from taking these supplements, but we would stress that there is no guarantee that they would be preventive or provide a decrease in symptoms.  The cost of these supplements are not high and there would not be great financial burden on the patient if she were interested in testing the effectiveness for these supplements in prevention and/or treatment of the common cold.