Common cold is one of most frequent infections which usually takes 1-2 weeks. Here i will present some evidence-based interventions which may shorten common cold duration and improve symptoms and backed by scientific data.
Zinc is a metal and metals can bind with other molecules to form chelated metal. Chelation of molecule will affect it function in some ways. Iron and Copper mostly involved in chelation of human specific molecules / proteins. In contrast, zinc chelates mostly non-human molecules and disturbing function of proteins / molecules essential for bacteria / viruses survival. Zinc ions presented in nasal / throat mucus support immunity response by killing / inhibiting vulnerable to chelation bacteria and viruses. Lets look at scientific publications.
Inhibition by zinc of rhinovirus protein cleavage (1976)
Zinc ions rapidly inhibit virus production in HeLa cells infected with human rhinovirus type 1A and lead to the accumulation of human rhinovirus type 1A precursor polypeptides. These results suggest that zinc complexes with rhinovirus coat proteins and alters them so that they cannot function as substrates for proteases or as reactants in the assembly of the virus particles.
Rhinovirus is most common cause of common cold and is being inhibited by zinc ions. But zinc affects other viruses.
Effect of Zinc Salts on Respiratory Syncytial Virus Replication (2004)
We sought to determine if zinc mediates a specific inhibitory effect against the major cause of pediatric lower respiratory tract disease, respiratory syncytial virus (RSV). We determined the in vitro inhibitory effect of three zinc salts (zinc acetate, lactate, and sulfate) on the replication of RSV at various concentrations of 10 and 1 mM and 100 and 10 μM. The inhibitory effect of zinc salts on RSV was concentration dependent and was not observed with other salts containing divalent cations such as calcium, magnesium, and manganese.
These are invitro studies, but invitro often does not replicate invivo. Lets explore few common cold trials evaluating effect of zinc. Most of them used zinc lozergents:
Although it is well recognized that most colds are caused by rhinoviruses, at least $37.5 million worth of antibiotics were prescribed for the common cold in 1994 in the United States. This acute respiratory disorder can be induced by more than 200 types of viruses, mainly human rhinoviruses. Other cold viruses infect people at varying times of the year; they include coronavirus, influenza virus, herpes simplex virus, respiratory syncytial virus, coxsackievirus, parainfluenza virus, picornavirus, paramyxovirus, adenovirus, and echovirus. Viruses are usually contagious during the first 3 days of symptoms. Rhinoviruses, which can cause cold symptoms year-round, have been implicated in most cases. More than 100 distinct rhinoviruses exist, making it impossible to produce a useful vaccine. Recent literature offers little support for the use of antihistamines to treat symptoms of the common cold. Review of six major studies on vitamin C supplementation gave no evidence that high-dose vitamin C supplementation decreases the incidence of the common cold.
In 1974, it was reported that zinc ions inhibit rhinovirus replication. It has been proposed that zinc ions interfere with rhinovirus protein cleavage, protect plasma membranes, attach to the surface of the rhinovirus, and interfere with the intercellular adhesion molecule 1 (I&W-l), the docking point for rhinoviruses on the surface of nasal epithelial cells.
The lozenges with zinc contained 9 mg of zinc in a 2.7-g dextrose base.
Overall symptom duration was significantly less in the zinc group than in the placebo group (mean, 3.8 day vs 5.1 days). Allergy-positive subjects who used zinc had a statistically significant shorter duration of nasal symptoms than allergy-negative subjects (3.5 days vs 7.6 days).
A review of subjects’ diary entries revealed that 4 subjects noted a chalky taste, 4 experienced a metallic aftertaste, and 3 complained of an upset stomach; none of the subjects noted a bitter taste. Most subjects liked the peppermint flavor.
If zinc-blocked viruses do not infect nasal tissue cells to replicate, the infectious process would be interrupted and the duration of the cold would be markedly shortened. Zinc is also believed to act as a protease inhibitor in its effect against rhinovirus infections. Other common cold-causing viruses inhibited by zinc ions include herpes simplex Virus and coxsackievirus.
Zinc has antibacterial activity. It can inhibit the growth of streptococci and actinomyces when used as a dentifrice. Zinc compounds have antiseptic, antifungal, and astringent properties
The effect seems to be large and practically valuable: reducing common cold symptoms from 5.1 to 3.8 days is a 1.3 / 3.8 = 34% reduction. There are some symptoms which accompany zinc usage: metallic taste and stomach upset.
Since there are more than 10 zinc common cold studies lets focus on meta-analysis / systematic reviews to get a wider picture:
Zinc Lozenges May Shorten the Duration of Colds: A Systematic Review 2011
Thirteen placebo-controlled comparisons have examined the therapeutic effect of zinc lozenges on common cold episodes of natural origin. Five of the trials used a total daily zinc dose of less than 75 mg and uniformly found no effect. Three trials used zinc acetate in daily doses of over 75 mg, the pooled result indicating a 42% reduction in the duration of colds (95% CI: 35% to 48%). Five trials used zinc salts other than acetate in daily doses of over 75 mg, the pooled result indicating a 20% reduction in the duration of colds (95% CI: 12% to 28%).
From here we can see that there might be a minimum threshold for zinc dosage, trials with 75mg and more show effect 20% - 40%. Non zinc-acetate forms seems to perform worse compared to zinc acetate.
Lets look at another meta-analysis which focused on 80mg+ zinc trials.
We analyzed three randomized trials on zinc acetate lozenges for the common cold administering zinc in doses of 80–92 mg/day.
Zinc acetate lozenges shortened the duration of nasal discharge by 34% (95% CI: 17% to 51%), nasal congestion by 37% (15% to 58%), sneezing by 22% (−1% to 45%), scratchy throat by 33% (8% to 59%), sore throat by 18% (−10% to 46%), hoarseness by 43% (3% to 83%), and cough by 46% (28% to 64%). Zinc lozenges shortened the duration of muscle ache by 54% (18% to 89%), but there was no difference in the duration of headache and fever.
From here we can see how different symptoms were affected by zinc intervention. There were three RCT analyzed - not too much, but enough data to shift view toward zinc have some positive effect versus no effect.
Zinc lozenges and the common cold (2017)
Seven randomised trials with 575 participants with naturally acquired common colds.
The dose of elemental zinc per lozenge ranged from 9 to 23.7 mg, and the average frequency of lozenge use ranged from 6 to 9.9 times per day.
The mean common cold duration was 33% (95% CI 21% to 45%) shorter for the zinc groups of the seven included trials. Three trials that used lozenges composed of zinc acetate found that colds were shortened by 40% and four trials that used zinc gluconate by 28%. The difference between the two salts was not significant: 12 percentage points (95% CI: −12 to + 36). Five trials used zinc doses of 80–92 mg/day, common cold duration was reduced by 33%, and two trials used zinc doses of 192–207 mg/day and found an effect of 35%. The difference between the high-dose and low-dose zinc trials was not significant: 2 percentage points (95% CI: −29 to + 32).
The lozenge of the Smith et al. trial contained mannitol and sorbitol. There is experimental evidence that mannitol and sorbitol bind zinc ions in the presence of saliva, which may explain the negative findings in the Smith et al. trial. It has been demonstrated that … mannitol/sorbitol inactivate zinc by chelation in saliva’ and ‘mannitol/sorbitol [zinc lozenge] formulations release no zinc ions when dissolved in the mouth’ referring to the Smith et al. trial.
Zinc ion can form complexes with a number of substances, which has caused substantial problems with the lozenge formulations in a few trials. Farr et al. used a lozenge that contained 2% citric acid, which binds zinc ions and very little or no free zinc is released from such lozenges. The low-dose (<75 mg/day) zinc lozenges studied by Douglas et al. contained tartaric acid and sodium bicarbonate, which bind zinc ions.The Turner trial had two low-dose zinc acetate trial arms. The zinc acetate lozenges contained hydrogenated palm-kernel oil, cotton-seed oil, and soy lecithin, and Eby pointed out that most probably those substances formed insoluble reaction products with zinc at the high preparation temperatures used in the production.
Nevertheless, the current evidence of efficacy for zinc lozenges, in particular zinc acetate lozenges, is so strong that common cold patients may be encouraged to try them for treating their colds.
Here we can see more evidence - 7 RCT, with high dosage (9-20mg 6-10 timer per day). Effect looks similar to previous studies / analysis and practically significant ~33%.
Combining summary on zinc:
My thoughts on these studies will be added later :)
A Clinical Trial of Hypertonic Saline Nasal Spray in Subjects With the Common Cold or Rhinosinusitis (1998)
Data were collected for 119 subjects. No difference was found in either primary outcome when hypertonic saline was compared with either normal saline or observation. Mean day of well-being was 8.3 (95% confidence interval [CI], 6.9-9.7), 9.2 (95% CI, 6.9-11.43), and 8.0 (95% CI, 6.7-9.3) days in the hypertonic saline, normal saline, and observation groups, respectively. Day 3 mean nasal symptom score was 3.8 (95% CI, 3.0-4.5) for hypertonic saline, 3.7 (95% CI, 2.9-4.5) for normal saline, and 4.1 (95% CI, 3.5-4.7) for observation. Only 44% of the patients would use the hypertonic saline spray again. Thirty-two percent noted burning, compared with 13% of the normal saline group (P=.05).
Conclusion Hypertonic saline does not improve nasal symptoms or illness duration in patients with the common cold or rhinosinusitis.
In a prospective, randomized, controlled, double-blind trial we compared the effectiveness of endonasal irrigations with Ems salt solution to that with sodium chloride solution in the treatment of adult patients with chronic paranasal sinus disease. Subjects (n = 40) were randomly allocated to treatment either with isotonic Ems salt solution or with isotonic sodium chloride solution. The treatment consisted of endonasal irrigation twice daily and additional nasal spray as required. Patients recorded rating scales of general discomfort, nasal airway obstruction, agreeableness of the irrigation, duration of improved nasal resistance after each irrigation, and the amount of additional nasal spray in a diary. Nasal air flow was not improved significantly. Subjective complaints, endonasal endoscopy, and radiography results revealed a significant improvement in both groups (P = 0.0001). In comparison, the two groups were not significantly different in outcome. Endonasal irrigations with salt solutions are effective in the treatment of chronic sinusitis, and a significant difference between Ems salt and sodium chloride was not observed.
Nasal irrigation for the alleviation of sinonasal symptoms (2001)
A total of 150 adult subjects with chronic sinusitis symptoms were recruited from the community and assigned to 1 of 3 treatment groups: nasal irrigation with bulb syringe, nasal irrigation with nasal irrigation pot, or control treatment with reflexology massage. Groups 1 and 2 performed daily hypertonic saline irrigation with 1 device for 2 weeks and then with the other device for 2 weeks. Group 3 performed reflexology massage daily for 2 weeks. Prospective data collected included pretreatment Medical Outcomes Study Short Form, pretreatment and posttreatment Rhinosinusitis Outcomes Measure, daily medication use, subjective treatment efficacy, and preference of irrigation method.
There was a significant and equivalent improvement in Rhinosinusitis Outcomes Measure 31 score after 2 weeks of intervention in each treatment group; 35% of subjects reported decreased use of sinus medication.
Efficacy of isotonic nasal wash (seawater) in the treatment and prevention of rhinitis in children 2007
We randomly assigned patients to 2 treatment groups, one with just standard medication, the other with nasal wash with a modified seawater solution (Physiomer) plus standard medication, and observed them for 12 weeks.
At visit 2, patients in the saline group achieved primary end points (measured on a 4-point numeric scale on which 1 indicated no symptoms and 4, severe symptoms) in the parameters nasal secretion and obstruction (mean scores vs nonsaline group, 1.79 vs 2.10 and 1.25 vs 1.58, respectively) (P < .05 for both). During the prevention phase (at visit 3, 8 weeks after study entry) patients in the saline group showed significantly lower scores in sore throat, cough, nasal obstruction, and secretion (P < .05 for all). By visit 3, significantly fewer children in the saline group were using antipyretics (9% vs 33%), nasal decongestants (5% vs 47%), mucolytics (10% vs 37%), and systemic antiinfectives (6% vs 21%) (P < .05 for all). During the same period children in the saline group also reported significantly fewer illness days (31% vs 75%), school absences (17% vs 35%), and complications (8% vs 32%) (P < .05 for all). Similar results were found at the final visit.
Conclusion: Children in the saline group showed faster resolution of some nasal symptoms during acute illness and less frequent reappearance of rhinitis subsequently.
Cochraine Review: Saline nasal irrigation for acute upper respiratory tract infections 2015
Most results showed no difference between nasal saline treatment and control. However, one larger trial, conducted with children, did show a significant reduction in nasal secretion score (mean difference (MD) -0.31, 95% confidence interval (CI) -0.48 to -0.14) and nasal breathing (obstruction) score (MD -0.33, 95% CI -0.47 to -0.19) in the saline group. However, a MD of -0.33 on a four-point symptom scale may have minimal clinical significance. The trial also showed a significant reduction in the use of decongestant medication by the saline group. Minor nasal discomfort and/or irritation was the only side effect reported by a minority of participants.
Authors' conclusions: Nasal saline irrigation possibly has benefits for relieving the symptoms of acute URTIs.
Inhibition of viral replication in the presence of chloride/halide salts was reported in the 1960’s
We have recently reported laboratory evidence that non-myeloid cells (e.g. epithelial, fibroblast and hepatic cells) have an innate immune mechanism, which is augmented in the presence of salt (NaCl). In cell culture models, DNA, RNA, enveloped and non-enveloped viruses are all inhibited in the presence of NaCl.
Here, we report the results of the Edinburgh and Lothians Viral Intervention Study (ELVIS), a pilot RCT of hypertonic saline nasal irrigation and gargling (HSNIG) versus standard care in adults with URTI (upper respiratory tract infection). We recruited 68 participants over 26 weeks.
80% in the intervention arm used 3% HS, while 9% each used 2.5%, 2% HS.
Amongst these, 56% were rhinovirus and 31% were coronaviruses (COV), with the rest due to enterovirus, influenza A virus, parainfluenza virus type 3 (PIV-3), respiratory syncytial virus (RSV) and human metapneumovirus (HMPV). We detected dual infections of rhinovirus with an enterovirus/COV HKU1 in two.
WURSS (Wisconsin Upper Respiratory Symptom Survey) 21 score was not significantly different between the two arms, probably a reflection in the sample size.
The intervention arm hence had a reduction in duration of illness by 1.9 days (95% CI = 0.4 to 3.3) (p = 0.01). The duration of illness was significantly lower (p = 0.01) even if the first day participants felt well was the end-point [Mean (SD) Intervention: 6.0 (2.4); Control: 8.0 (3.4) days]. Participants performed HSNIG for a median of 5 days (IQR: 3 to 6) and at a median of thrice a day (IQR: 2 to 3)
Chen et al. enrolled 61 children with allergic rhinitis (moderate to severe) with mean age of 6 years (range from 2 to 15 years) for daily nasal irrigation as an adjunct treatment to their intranasal corticosteroid. Daily nasal irrigation with seawater significantly improved the symptoms of the allergic rhinitis, proving its effectiveness in controlling symptoms and reducing the dose of a nasal corticosteroid. Friedman et al. compared the efficacy of Dead Sea salt irrigations and nasal spray versus saline irrigations and topical nasal steroid spray in the treatment of symptoms of chronic rhinosinusitis. Treatment with Dead Sea salt irrigations and sprays provides significant improvement in symptoms and quality of life for patients with chronic rhinosinusitis and appears to be as effective as using a combination of a topical intranasal steroid and hypertonic saline solution.
For now i just present studies, will add my thoughts later.