Viral Upper Respiratory Infection

Humanity’s most frequent illness, the common cold, is caused by acute viral infection of the upper respiratory tract.1, 2, 3, 4 Acute respiratory infections (ARIs) are often classified as being caused either by influenza, the most serious of the common viruses, or other viruses (noninfluenza ARI). In the United States, noninfluenza ARI accounts for more than 20 million clinic visits and 40 million lost days of school and work, with total costs estimated at $40 billion, making noninfluenza ARI the seventh most expensive illness.5, 6, 7 Influenza causes an annual mid-winter epidemic that varies year to year, but can be a major cause of hospitalization and death.8, 9, 10

Although colds are often considered a nuisance rather than a major public health threat, even rhinovirus, the least pathogenic of the common cold viruses, may cause death among elderly and immunocompromised individuals.11, 12, 13

On average, children experience four to six symptomatic colds per year, in addition to several asymptomatic infections. For adults, the average is two to three symptomatic colds per year and perhaps one or two asymptomatic infections.14, 15, 16 Some individuals are particularly prone to colds, whereas others get them infrequently.¹⁷ Numerous factors appear to be involved, but overall, susceptibility remains poorly understood.

Although there still is no good proven cure for the common cold, a number of treatments have been reported to have symptom-reducing benefit in one or more randomized controlled trials (RCTs).18, 19, 20, 21, 22, 23, 24 In terms of prevention, behavioral strategies such as hand washing, regular exercise, and smoking avoidance are widely accepted to be at least somewhat effective.25, 26, 27, 28, 29, 30, 31 Immunization is considered impractical, as there are hundreds of strains of viruses. Our own research indicates training in mindfulness-based stress reduction may serve to reduce incidence, duration and impact of viral ARI.32, 33, 34, 35, 36

Pathophysiology

As an illness, the common cold is characterized by nasal congestion and drainage, sneezing, sore or scratchy throat, cough, and general malaise.37, 38, 39 Cough may or may not be present and tends to occur later in the disease, occasionally lasting for weeks after other symptoms have resolved. The severity of symptoms varies markedly, from barely noticeable to truly debilitating.⁴⁰ While true fever is atypical for most viruses, feelings of feverishness and chilliness are common.⁴¹

There is no proven cure for the common cold. Even the most positive previous trials have reported only modest symptomatic benefit, with little or no duration of benefit.

As an infectious disease, viral ARI is characterized by the replication of viruses in the nasopharyngeal epithelium,⁴² leading to a cascade of local and systemic immune responses.43, 44, 45 Viral replication triggers cytokine-mediated local inflammatory reactions, in addition to the recruitment of white blood cells. Parasympathetic neural pathways activate and coordinate local responses. Blood vessels dilate and capillaries leak, causing edematous tissue and transudates in the nasal passages.⁴⁶ Mucous glands are activated, resulting in mild to copious exudative discharge. Inflammatory changes in the respiratory epithelium may persist for days or weeks after viral shedding dies down. Activation of inflammatory mechanisms leading to bronchial constriction makes viral ARI the most frequent cause of asthma exacerbation.⁴⁷

Rhinovirus is the single most common etiological agent, but accounts for less than half of all ARIs.48, 49, 50 Other causative viruses include adenovirus, coronavirus, enterovirus, influenza virus, parainfluenza, and respiratory syncytial virus (RSV).4, 51 Metapneumovirus52, 53 and bocavirus54, 55, 56 are now known to cause ARI illness in both children and adults. There are likely additional viruses that are as yet undiscovered; even the best research laboratories fail to identify an etiological agent in up to one quarter of individuals with obvious colds. A small number of bacteria, such as streptococcus and Haemophilus influenza, may cause common cold syndrome.

Respiratory viruses follow seasonal patterns. Influenza and RSV infections only occur during the winter months, with rhinovirus colds typically observed in the fall and spring. Adenovirus infection appears year-round. Parainfluenza mini-epidemics are episodic, while sporadic outbreaks of atypical agents, such as Bordetella pertussis, further complicate the epidemiology of ARI.

The spectrum of illness varies greatly within and among agents. In general, influenza causes the most severe illness and is therefore often classified separately from other viral ARIs. Nevertheless, the majority of illness episodes caused by influenza are indistinguishable from those caused by other viruses, with a significant number of influenza infections reported to be asymptomatic.57, 58, 59, 60, 61, 62 Less than a quarter present with the classic “influenza-like illness” symptoms of rapid onset, fever, cough, headache, and myalgia. Despite a coordinated system to provide influenza vaccine (flu shots) each fall, influenza is implicated in as many as 20,000 deaths each year.8, 9, 63

Psychosocial Influences

Common colds are influenced by a variety of biological, psychological, and social factors. Numerous cross-sectional and prospective epidemiological studies have provided relatively consistent findings.14, 15, 16 Colds occur most frequently among infants and children, and among adults in contact with them. Children who are in preschool daycare have more colds than those who are not, but have fewer colds during subsequent school years.64, 65 While moderate regular exercise protects against infection, excess activity, such as running a marathon, increases risk temporarily.31, 66, 67, 68 Poor mental health has been shown to be associated with increased risk.69, 70 Stress, both acute and chronic, is known to increases ARI risk.71, 72, 73 Sheldon Cohen first demonstrated this by showing that perceived stress predicted not only whether volunteers would become sick when exposed to rhinovirus, but whether and to what extent they would shed virus.74, 75, 76 Childhood socioeconomic status,⁷⁷ number and quality of social relationships,⁷⁸ and negative emotion79, 80 have also been shown to predict viral shedding, as well as severity and duration of cold symptoms. Subsequent studies have corroborated these findings.62, 71, 81, 82, 83, 84 Building on this background, my research team conducted a randomized trial finding that training people in mindfulness-based stress reduction can lead to substantive reductions in ARI illness episodes.32, 33, 34, 35, 36 An earlier study by Dr. Rakel and I on placebo effects and the influence of doctor–patient interaction indicated that empathetic patient-oriented clinicians may be able to positively influence common cold outcomes.⁸⁵

The common cold is an excellent example of how the mind and body interact. Stress can increase susceptibility while social support can reduce incidence. Perceived empathy of caregivers may also reduce illness severity and duration.

Integrative Therapies

There are hundreds of reported treatments for the common cold.18, 19, 20, 21, 22, 23, 27, 86 Globally, botanical remedies have been the mainstay of treatment. Descriptions of herbal therapies for common cold fill countless pages of notes and treatises by physicians, anthropologists, and ethnobotanists.87, 88, 89, 90 However, relatively few of these traditional remedies have been adequately tested for pharmaceutical properties and clinical effectiveness. The present section will review several botanicals that are widely used or have been evaluated by randomized controlled trials (RCT). The next section will cover the use of nonbotanical complementary treatments, such as vitamin C and zinc. Finally, this chapter will briefly describe conventional therapies, such as antihistamines, decongestants, and cough medications.

Botanicals

Andrographis(Andrographis paniculata or Justicia paniculata)

Andrographis is indigenous to Asia, with traditional use most prominent in India. Of the 28 Andrographis species, A. paniculata is most commonly used for the treatment of ARI. According to Ayurvedic tradition, Andrographis is attributed to many important medicinal properties and is used for the treatment of constipation, digestion, fever, pain, sore throat, snake bite, and to clean the blood. In the West, andrographis is most commonly used as a common cold treatment or preventative.

Various laboratories have reported antimicrobial,⁹¹ antihyperglycemic,92, 93 antiinflammatory,⁹⁴ immunomodulatory,95, 96 and psychopharmacological⁹⁷ effects attributable to andrographolide, flavonoids,⁹⁸ and other phytochemical constituents. There have now been at least eight RCTs published including more than 1000 subjects that have evaluated various andrographis derivatives in the treatment of ARI, including pharyngitis.99, 100, 101, 102, 103, 104, 105, 106 Systematic reviews by Coon and Ernst¹⁰⁷ and Poolsup et al.¹⁰⁸ conclude the following:

“Collectively, the data suggest that A. paniculata is superior to placebo in alleviating the subjective symptoms of uncomplicated upper respiratory tract infection. There is also preliminary evidence of a preventative effect. A. paniculata may be a safe and efficacious treatment for the relief of symptoms of uncomplicated upper respiratory tract infection; more research is warranted.”¹⁰⁷

“Current evidence suggests that A. paniculata extract alone or in combination with A. senticosus extract may be more effective than placebo and may be an appropriate alternative treatment of uncomplicated acute upper respiratory tract infection.”¹⁰⁸

The most recent trial, not included in the reviews referred to previously, also reported positive results.¹⁰⁹ Based on published evidence, and with no evidence of serious safety concerns, it seems reasonable for adults to seek relief from ARI symptoms with andrographis-based cold remedies. There is insufficient evidence to favor specific products, dosing regimen, or particular standardization procedures for phytochemical content. For pregnant women and children, it seems prudent to recommend against the use of andrographis because there is little data from studies in these populations to exclude risk of harm.

Dosage and standardization

The majority of clinical trials used products standardized to 4 or 5 mg andrographolide per tablet. A reasonable dose regimen would be two to four of these tablets, three times daily, for the first few days of a cold.

Precautions

There are no known side effects of andrographolide; however, as with all medicinal treatments, caution and careful use are recommended.

Astragalus (Astragalus membranaceus; Astragalus mongholicus)

Astragalus is an important medicinal plant in traditional Chinese medicine.¹¹⁰ While there are dozens, if not hundreds, of reported uses, astragalus extracts are commonly used for both the treatment and prevention of the common cold.¹¹¹ While antiviral activity has been reported, immunomodulation is the purported mechanism of action. Indeed, several studies have reported the effects of astragalus on the immune system, from enhanced immunoglobulin production to restoration of lost T-cell activity.112, 113, 114, 115, 116 Astragalus root contains astragaloside, flavonoids, and saponins, which are variously thought to be involved in various hypothesized mechanisms of action. Unfortunately, due to a lack of human ARI trials, no clear recommendations can be made for or against the use of astragalus for the treatment or prevention of common cold, and no specific doses or precautions have been reported.

Carrageenan

Carrageenans are linear sulfated polysaccharides deriving from Irish moss (Chondrus crispus) and other seaweed and algae. Carrageenans are widely used in the food and cosmetics industry for the thickening, stabilizing, and gelling of a wide variety of products, including toothpaste. During the past decade, a carrageenan-based nasal spray has been tested as common cold treatment, with positive results reported.¹¹⁷ Eccles et al. reported reductions in inflammatory cytokines levels and symptoms in a randomized trial among N = 35 young adults.¹¹⁸ Fazekas et al. reported an RCT among N = 153 children, which found reductions in viral load and time to viral clearance, but no symptomatic benefit.¹¹⁹ Ludwig et al. reported an RCT among N = 211 adults, where “alleviation of symptoms was 2.1 days faster in the carrageenan group in comparison to placebo (p = 0.037).” It appears that all of these studies were sponsored by the same company, Marino Med, and that their product is available in Europe but not the United States. While these results are certainly intriguing and carrageenan nasal spray is likely safe, further research is required before specific recommendations can be made regarding its use for the treatment of URI.

Dosage

The formulation used in the trial above was Iota-Carrageenan (0.12%) in a saline solution, one spray in each nostril, three times daily for 4 days.

Chamomile (Matricaria chamomilla; Matricaria recutita, German chamomile; Chamaemelum nobile, Roman chamomile)

Chamomile has been used widely as a botanical remedy for centuries for a variety of purposes, including dysmenorrhea, gingivitis, hemorrhoids, infantile colic, indigestion, insomnia, nausea, vaginitis, and topically, for a variety of skin conditions.¹²⁰ In the United States, chamomile is most often used as a calmative or sedative, and for the treatment of irritable bowel syndrome. However, chamomile is also used for acute respiratory infection and hence merits inclusion in the present review. As a common cold remedy, chamomile can be taken as an infusion (chamomile tea) or as an inhalation by boiling the flowering tops. A study evaluating inhaled vapors from boiling chamomile reported benefit but was of insufficient quality to reach firm conclusions.¹²¹

Dosage

Although there is limited evidence, a cup or two of chamomile tea as supportive treatment for the common cold is safe and may be beneficial.

Precautions

While there are no known dose-dependent adverse reactions, allergic sensitivity, including several cases of anaphylaxis, has been reported.¹²²

Echinacea (Echinacea angustifolia; Echinacea purpurea; Echinacea pallidae)

All dozen species from the genus Echinacea are indigenous to North America. Native communities discovered many medicinal uses, later transferring their knowledge to European settlers.¹²³ In the 1920s, Echinacea was introduced into Germany, where it has been popular ever since. Today, echinacea extracts are widely used in America, Europe, and elsewhere, particularly for the prevention and treatment of the common cold.¹²⁴ A considerable body of evidence exists regarding the uses of echinacea, including 24 randomized trials including more than 3000 participants,¹²⁵ and dozens of in vitro and animal studies.126, 127, 128 While there is consensus that various echinacea extracts display immunologic activities, such as promoting macrophage activation and inducing cytokine expression,129, 130, 131, 132, 133, 134, 135, 136, 137 there is considerable disagreement concerning which of the many echinacea-derived phytochemicals are involved. Various alkylamides, glycoproteins, polysaccharides, and caffeic, cichoric, and caftaric acids have all been implicated. Differing extracts from all three species and from various plant parts have shown immunoactivity in laboratory models. To my knowledge, no credible head-to-head, dose-finding, or viral load outcome studies have been reported, with very little pharmacokinetic information available.138, 139 A comprehensive safety review notes a number of reported allergic reactions but suggests no dose-dependent adverse effects or major drug interaction concerns.¹⁴⁰

Randomized clinical trials testing echinacea extracts for the prevention and treatment of common cold were first conducted in Europe, with several early trials reporting positive result.141, 142, 143, 144, 145, 146, 147, 148 More recent trials in the US and elsewhere have reported mixed results, with higher quality trials finding no benefit.149, 150, 151, 152, 153 I directed two of those trials. The first was flatly negative¹⁵⁴; however, the second observed some positive trends.¹⁵⁵ Preventive trials have all trended in beneficial directions, but none have individually demonstrated clearly positive results.¹⁵⁶ Systematic reviews of the two dozen reported trials vary in their interpretation of the evidence.157, 158, 159, 160, 161, 162, 163 Our recent Cochrane review¹²⁵ and JAMA publication¹⁵⁶ found no clear benefit among treatment trials but noted that prevention trials consistently favored some benefit. Not included in those reviews, a recent head-to-head trial of an echinacea tea against the antiinfluenza drug oseltamivir in influenza-like illness found the echinacea preparation to be equally effective.¹⁶⁴ A recent review argued that positive trials may be due to inadvertent unblinding, with either placebo effect or participant reporting bias contributing to false positive results.¹⁶⁵ It is also possible that negative studies have gone unreported, thereby yielding publication bias.

Given that echinacea extracts appear safe and that the vast majority of published trials have reported positive trends, it seems reasonable to cautiously support the use of echinacea in adults, particularly those with favorable personal experience and positive expectations.¹⁶⁶

Dosage and standardization

Positive trials have used differing formulations, with preparations made from the leaf and flower of Echinacea purpurea most widely used. However, preliminary evidence suggests that alkylamides from the roots of E. purpurea and E. angustifolia may have the greatest bioavailability and immunoactivity.139, 167, 168 While there is a lack of consensus regarding standardization criteria, the majority of experts agree that echinacea extracts should be used as early as possible in the course of a cold, with multiple doses per day for the first few days of symptoms. Beyond that, no specific doses or precautions have been identified.

Precautions

My own opinion is that use in children should be discouraged, as the best pediatric RCT found no positive effects but did report a slight increase in the incidence of skin rash among patients randomized to echinacea.¹⁶⁹ While there is a modest case control study finding no adverse effects in pregnancy,¹⁷⁰ I caution against its use as the risks are theoretically substantive.

There is greater evidence regarding echinacea, zinc, and vitamin C than any single conventional therapy. Unfortunately, there is a negative trial for every positive one.

Elderberry (Sambucus nigra)

Preliminary research indicates elderberry extracts may have antiinflammatory and antiviral antiinfluenza properties.171, 172, 173 A Norwegian RCT among N = 60 volunteers reported potential symptom reduction benefit in influenza-like illness.¹⁷⁴ To my knowledge, those findings have not been replicated. With only one small limited trial and no good safety data, the use of elderberry for the treatment of URI is intriguing but unlikely to become widely adopted.

Garlic (Allium sativum)

Garlic is widely used as a food and flavoring. Medicinally, there are hundreds of reported uses of garlic. The most prominent of these is moderation of cholesterol and other lipids, for which modest beneficial activity has been reasonably established.175, 176, 177, 178 While in vitro studies have reported antibacterial and antiviral effects, only one relevant human trial of the efficacy of garlic in treating the common cold has been reported.¹⁷⁹ Josling reported a RCT in which 146 participants were randomized to daily garlic or placebo capsules for 12 weeks.¹⁸⁰ Dramatic between-group differences were observed, with 65 colds in the placebo group and 24 in the garlic group (p < 0.001), with an average cold duration of 5.0 days among those taking placebo versus 1.5 days among those taking garlic (p < 0.05). While the study was reportedly double-blind, proof of blinding was not provided. The active treatment was “an allicin-containing garlic supplement” dosed at “one capsule daily.” No further information on extraction methods, phytochemical composition, or amount of garlic was provided. Nevertheless, it may be reasonable to tentatively support the use of garlic as the risk of side effects is low, cardiovascular benefits are likely, and garlic is tasty.

Dosage

My personal recommendation is to use fresh garlic in cooking as much and often as palatable while being conscious of the cardiovascular and cold-prevention benefits of garlic.

Ginger (Zingiber officinale)

Ginger root is also very widely used as a food flavoring as well as for its medicinal properties. There is reasonable evidence supporting its effectiveness as an antinausea agent181, 182, 183 and in the treatment of vertigo,¹⁸⁴ dysmenorrhea,185, 186, 187 and knee osteoarthritis.¹⁸⁸ In the ARI setting, one small trial of a ginger and goldenrod combination reported small benefits.¹⁸⁹

To my knowledge, no other trials of ginger root in the treatment of URI have been completed. Nevertheless, as ginger is widely used as a treatment for colds and flu, and as I personally happen to use ginger as a common cold remedy, it is included in this review.

Dosage

Buy a nice ginger root at the local grocery store, shave off the peel and slice the root thinly using a sharp knife, being careful not to cut one’s fingers. Drop the sliced ginger into boiling water and steep for 5 minutes, then add honey and lemon to taste. Sip slowly, and feel the ginger work! (Dr. Barrett’s personal recipe)

Ginseng (Panax ginseng, Panax quinquefolium)

Asian (P. ginseng) and American (P. quinquefolium) ginseng are used for a wide variety of purposes. The genus name Panax, chosen by Linnaeus, in fact derives from the same root word as Panacea, the Greek goddess of healing. The most widespread medical theory supporting the use of ginseng derives from traditional Chinese medicine.¹⁹⁰ Ginseng is thought to have “adaptogenic” attributes, which bring balance, homeostasis, and healing.191, 192, 193 Some evidence of the effectiveness of a P. ginseng extract in preventing common cold comes from an Italian trial among N = 227 individuals followed for 12 weeks.¹⁹⁴ A Korean preventive trial evaluating P. ginseng among N = 100 individuals reported 12 cases of ARI (25%) in the ginseng group, compared to 22 (45%) in the placebo group.¹⁹⁵ A series of Canadian studies of a polysaccharide-rich P. quinquefolium extract reported immunomodulatory changes.196, 197, 198 An RCT among N = 198 elderly nursing home residents reported reductions in both cold and flu episodes.¹⁹⁹ A second preventive trial using the same formulation among N = 323 subjects reported a statistically significant 13% difference in incidence in cold and flu episodes during 4 months of observation.200, 201 The proprietary formula used in this series of research has been approved for use in Canada. In the U.S., it would seem reasonable for preventive-minded people to use small doses of ginseng extracts (either P. ginseng or P. quinquefolium) regularly during the cold and flu season; however, as evidence is modest and safety not established, the use of ginseng in pregnancy and among children is not advised. Evidence is insufficient to recommend specific dosing or side effects.

Dosage

For prevention during times of high risk, take 100 mg daily. For acute infection, consider 100 mg twice daily for 9 days.

Precautions

Ginseng is generally well tolerated but may cause insomnia, tachycardia, and elevated blood pressure.

Goldenseal (Hydrastis canadensis)

Goldenseal is among the top selling botanicals in the United States. In addition to cold remedies, Hydrastis extracts are found in treatments for allergy and in digestive aids, feminine cleansing products, mouthwashes, shampoos, skin lotions, and laxatives.¹²⁰ Goldenseal is combined with echinacea in many cold therapies. However, there are currently no RCTs evaluating the efficacy of goldenseal, either alone or in combination with echinacea. The phytochemical constituent berberine is pharmacologically active, and in overdose can cause significant toxicity, including cardiac arrhythmia and death.²⁰² Goldenseal is contraindicated in pregnancy and lactation. Berberine-rich extracts are included in many traditional Chinese medicines. The demand for goldenseal has led to overharvesting and to the substitution of other plants containing berberine or similar compounds. Given these considerations, I do not recommend goldenseal for the prevention or treatment of the common cold.

Lemon (Citrus limon)

Originally from India, the lemon tree is now cultivated throughout the world and used as a food, flavoring, and botanical remedy. Medicinal uses include the prevention and treatment of scurvy. Lemon is also used for malaria, rheumatic arthritis, and fever, in addition to numerous other indications. Lemon juice and lemon-flavored teas are used for the prevention and treatment of colds, coughs, and flu. While rigorous evidence of the effectiveness of lemon is lacking, lemon is generally recognized as safe and to have important nutritional value as a source of vitamin C (ascorbic acid), thereby making lemon a good choice for those who derive symptomatic comfort.

Peppermint (Mentha piperita)

Peppermint and other members of the mint family are widely used for a variety of medicinal purposes, including coughs and colds, as well as for a variety of gastrointestinal purposes. When treating colds, mint teas and infusions are taken internally, while mint oils are applied topically. Peppermint oil is composed primarily of menthol, menthone, and menthyl acetate. Menthol especially has been extracted and included in various topical cold remedies classified as “menthol rubs.” While neither mint teas nor menthol rubs have been subjected to rigorous randomized controlled trials evaluating their efficacy in treating the common cold, both applications seem reasonable from a cost, risk, and potential benefit perspective, at least in adults. More concentrated preparations, such as peppermint oil, should not be applied to the mucosa of infants or young children, as direct inflammatory toxicity can result. Bronchospasm, tongue swelling, and even respiratory arrest have been rarely reported.202, 203

Umckaloabo (Pelargonium sidoides)

Various preparations of this South African plant have been used for centuries following ethnobotanical tradition.204, 205, 206, 207 Antiviral effects, including antiinfluenza activity, have been reported.208, 209 Three RCTs in adults (N = 746) and three RCTs in children (N = 819) have yielded somewhat inconsistent yet generally positive findings.210, 211, 212 A 2013 Cochrane review concluded that “P. sidoides may be effective in alleviating symptoms of acute rhinosinusitis and the common cold in adults, but doubt exists. It may be effective in relieving symptoms in acute bronchitis in adults and children, and sinusitis in adults.”²¹³ Scientific interest in Pelargonium is relatively recent, and conclusions to date are tentative. However, umckaloabo seems a reasonable choice for adults looking for a natural treatment for cough, cold, or bronchitis. No specific formulation or dose regimen can be recommended.

Dosage

The formulation used in the above research was Eps 7630, which is an 11% aqueous ethanolic extract available in Europe. In America, the most commonly available form is a 1X homeopathic dose through a variety of brand names. The effectiveness of homeopathic doses is unknown.

Precautions

While no dose-dependent adverse effects are known, gastrointestinal disturbance and hepatotoxicity have been reported,²¹⁴ and the results of a previous study indicated that allergic reactions may be a relatively frequent problem.²¹⁵

There are several trials supporting the use of Andrographis, pelargonium (umckaloabo), and intranasal carrageenan gel. These are ones to watch!

Vitamins, Minerals, and Home Remedies

Chicken Soup

Hot chicken soup is the epitome of traditional cold remedies, and its use is supported by many personal testimonies. Chicken soup as a cold remedy is somewhat supported by at least two human studies, one reporting inhibited neutrophil chemotaxis²¹⁶ and the other indicating increased nasal mucus velocity and decreased nasal airflow resistance.²¹⁷ No RCTs using patient-oriented outcomes have been reported. Personally, I would be much more enthusiastic if the chicken industry adopted more responsible sanitary, environmental, and animal welfare policies. In the meantime, the use of soup made from free-range chickens and substantial quantities of wholesome organic vegetables can be cautiously supported, although I personally prefer soup with vegetables only.

Honey

Honey is widely used as a food and flavoring, and has been advocated as a treatment for cough and other ARI symptoms, particularly for children. A 2012 Cochrane review found two trials including 265 children.218, 219, 220 While the quality of the trials was considered mediocre, the authors concluded that “honey may be better than ‘no treatment’ and diphenhydramine in the symptomatic relief of cough but not better than dextromethorphan.”²¹⁸ These may not be fair comparators, as diphenhydramine is not known to have antitussive properties and dextromethorphan and other OTC drugs are not recommended for children.²³ Nevertheless, honey may be a reasonable choice for cough in children aged 2 to 10 years as it is safe and tastes good. Honey does contain large amount of glucose and fructose, so tooth-brushing afterwards is recommended. Honey is not recommended for infants due to the risk of Clostridium botulinum infection.

Dosage

Consider adding a teaspoon of honey to ginger, chamomile, or peppermint tea.

Consider adding a teaspoon of honey for cough and a squeeze of lemon to a tea made with one or more of the botanicals discussed as having positive evidence against viral URI.

Dry Saunas and Hot Baths

In 1990, Ernst et al. reported a nonrandomized 6-month prevention trial in which, “25 volunteers were submitted to sauna bathing, with 25 controls abstaining from this or comparable procedures. In both groups the frequency, duration and severity of common colds were recorded for 6 months. There were significantly fewer episodes of common cold in the sauna group. This was found particularly during the last 3 months of the study period when the incidence was roughly halved compared to controls. It is concluded that regular sauna bathing probably reduces the incidence of common colds, but further studies are needed to prove this.”²²¹ The research community apparently did not heed Dr. Ernst’s sage advice as, to my knowledge, there have been no subsequent trials testing the therapeutic properties of hot water bathing in the prevention or treatment of common cold. However, in 2010, Pach et al. reported a trial evaluating hot dry sauna as a treatment for the common cold, in which N = 157 individuals were randomized to wearing a winter coat in a hot dry sauna or wearing a coat in the sauna at room temperature.²²² Trends towards symptomatic benefit and reduced medication use were noted at various time points during the 7 days of treatment; however, the overall conclusion was that “inhaling hot air while in a sauna has no significant impact on overall symptom severity of the common cold.”²²² Despite the limited research on hot baths and the disappointing results of the previous dry sauna trial, these are modalities that I would personally recommend, should the opportunity exist, as long as one is reasonably healthy and the facilities are clean. However, I do not recommend wearing a winter coat in the sauna as I do not consider this proper attire. An optional bathing suit may perhaps be more appropriate, and certainly easier for laundering. There is no data regarding the optimal frequency, duration, or temperature of saunas and baths for the prevention or treatment of URI.

Precautions

Although saunas and hot baths are generally safe and potentially therapeutic, adequate hydration and care when standing up are important because heat-induced peripheral vasodilation can lead to orthostatic hypotension, dizziness, and increased fall risk.

Inhaled Hot Moist Air

One widespread traditional cold remedy involves the inhalation of hot moist air, often with a botanical or other additive. As noted above, benefits of inhalation of vapors from chamomile tea were reported by a previous clinical trial.¹²¹ The most recent Cochrane review evaluated six heterogeneous RCTs with a total of 394 trial participants reporting mixed results.²²³ While it seems reasonable to recommend humidification when the air is dry, and perhaps advocate the inhalation of hot moist air for those that find it comforting, it should be noted that water boils at around 100 °C, and inhalation of vapors near this temperature may cause significant thermal damage. Be careful!

Hot Toddy

I have been impressed by the number of people, including several physicians, who have come up after a lecture to tell me that their favorite cold remedy was some form of a hot alcoholic beverage, such as a “hot toddy” or hot buttered rum. While to my knowledge no trials have tested any of these remedies, testimonies of symptomatic benefit should not be totally disregarded. At a societal level, there is a well-known inverse relationship between moderate regular consumption of alcoholic beverages and the number and severity of colds.²⁸ Those who consume one or two drinks daily have fewer and less severe colds than both those who drink heavily and fewer colds than those who do not drink alcohol at all. One study found this relationship to be most pronounced for red wine.²²⁴ Personally, I like to add a bit of rum to a cup of hot orange juice as a nighttime cold remedy. However, this would be contraindicated among those with alcohol use disorders, in children, pregnant women, and individuals who need to use a motor vehicle or who operate hazardous machinery.

Nasal Saline

What could be more healthful and therapeutic than a mild saltwater rinse of the nasal cavities? While saline nasal lavage is a longstanding tradition in many cultures, it is only recently that Western biomedicine has begun to integrate this practice. Currently, there are a number of positive trials among individuals with allergic rhinitis and chronic sinus symptoms, including one at the University of Wisconsin Department of Family Medicine.²²⁵

A 2015 Cochrane review evaluated the results of five RCTs, two in adults (N = 205) and three in children (N = 544), all comparing nasal saline to routine care of common cold.²²⁶ These authors concluded, “nasal saline irrigation possibly has benefits for relieving the symptoms of acute URTIs. However, the included trials were generally too small and had a high risk of bias, reducing confidence in the evidence supporting this.” In the largest adult trial, Adam et al. randomized 140 individuals to one of three groups: hypertonic saline, normal tonic saline, or no treatment (two squirts per nostril, three times per day.) No significant differences were observed between groups in terms of duration or severity of symptoms.²²⁷ On the other hand, the largest pediatric trial published to date reported significant improvements in breathing and reductions in nasal secretions.²²⁶ In addition to trials designed to test nasal saline, there is some evidence from trials using saline as a placebo. For example, Diamond et al. reported a trial in which 955 participants were randomized to one of three doses of nasal ipratropium, to the “placebo” saline vehicle, or to no treatment at all.²²⁸ The nasal saline vehicle yielded greater benefit compared to no treatment than did any of the ipratropium doses when compared with each other or with saline.

Overall, nasal saline is a remedy with potential benefit and virtually no cost or significant risks. I suggest twice daily treatment for the first few days of a cold (see Chapter 113).

Probiotics

Probiotics are live bacteria that are thought to support healthy gastrointestinal function. Several trials have demonstrated benefit for antibiotic-associated diarrhea²²⁹ and have indicated benefit for irritable bowel syndrome and other conditions.230, 231, 232, 233, 234 Interestingly, there is now reasonably strong preliminary evidence that probiotics may also prevent or ameliorate ARI illness. This evidence includes more than a dozen trials testing the efficacy of probiotics in preventing cold and flu illness episodes.235, 236, 237, 238, 239, 240, 241, 242, 243 One RCT was conducted among elderly individuals,²⁴⁰ and two involved children.239, 242 One of these was aimed at preventing diarrheal illness but instead provided evidence of cold and flu prevention.²⁴² Two recent meta-analyses reviewed more than a dozen RCTs including more than 3000 participants and noted “significantly fewer numbers of days of illness per person”²⁴⁴ among those receiving probiotics versus placebo, concluding that “the results implied that probiotics had a modest effect in common cold reduction.”²⁴⁵ Various formulations are available without prescription and, to my knowledge, there are no significance concerns regarding adverse effects. Until further evidence becomes available, we can be cautiously optimistic and perhaps even advocate probiotics for preventing or treating common cold; however, no specific products or dose regimens can be singled out as particularly effective (see Chapter 105).

Vitamin C (Ascorbic acid)

The use of vitamin C for the prevention and treatment of the common cold became widespread after double Nobel laureate Linus Pauling promoted his belief in this therapy in the 1950s and 1960s.²⁴⁶ By the early 1970s, three major trials conducted in Toronto by T.W. Anderson indicated preventive effectiveness.247, 248, 249 Over the next few decades, more than 30 trials including more than 12,000 participants have been reported.250, 251 Interestingly, approximately half of these trials reported positive results, far more than would be expected by chance; however, this was not enough to convince more skeptical scientists. While there is no clear consensus regarding the reasons why some trials found benefit and others did not, it seems reasonable to tentatively conclude some preventive effectiveness, as concluded by a recent Cochrane systematic review:

“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.”²⁵⁰

The evidence supports modest preventive effectiveness for doses of 200 mg to 500 mg daily. Benefits of larger doses for prevention, or as treatment for new onset colds, is supported by some trials and systematic reviews,²⁵² while other trials have reported contradictory results.²⁵³ Given the generally accepted safety of ascorbic acid at doses up to a few grams per day over short periods, it seems reasonable to cautiously support its use in treating URI, particularly among individuals those positive experiences and expectations (very high doses, such as the 18 grams per day that Linus Pauling was reportedly taking up to his death at age 93 in 1994, have not been tested in trials and cannot be supported). Regular intake of vitamin C rich foods, however, can be enthusiastically supported because greater intake of fresh fruits and vegetables has been associated with many health benefits in dozens of large observational studies and has no known risks.

Vitamin D

In combination with calcium, vitamin D is widely recommended as a preventive or treatment for osteopenia and osteoporosis. Interest in vitamin D for a wide variety of other health concerns has blossomed over the past decade. Vitamin D for common cold prevention and treatment has been advocated, bolstered by the fact that vitamin D levels are low and ARI incidence is high during winter months.²⁵⁴ Unfortunately, enthusiasm has not been matched by evidence. To my knowledge, there is only one good quality RCT evaluating vitamin D for preventing colds.²⁵⁵ Although the results trended towards slight benefit, the general interpretation was negative.²⁵⁶

Zinc

In some ways, the story of zinc for the treatment of colds is similar to that of vitamin C. Reportedly, the physician George Eby noticed rapid recovery from an ARI in a child hospitalized and given zinc for unrelated reasons. This observation was followed by an RCT that reported positive results in 1984 (but had methodologic flaws).²⁵⁷ Since then, a dozen trials with more than 1300 participants have been conducted using various zinc preparations.258, 259, 260, 261, 262, 263 Trials testing zinc acetate in doses of 75 mg or more have tended to report the most positive results.²⁶⁴ The most recent Cochrane review was generally positive,²⁵⁹ and many authorities now recommend zinc as a treatment for common cold.²⁶⁵ However, there are concerns regarding adverse effects, such as unpleasant taste and/or nausea. While zinc is an essential mineral, with many known protective effects when ingested in foods in appropriate doses,266, 267 use of relatively high doses during acute illness may confer minimal risks. Advocates recommend frequent dosing (every 2 to 3 hours) for the first 2 or 3 days of a cold, a dosing regimen that some patients may not find convenient. Nasal irritation is common, and loss of sense of smell has been reported.²⁶⁸ My personal recommendation is to tentatively support the use of oral or nasal zinc preparations among those who have experienced benefit and/or express positive feelings about the treatment but to not recommend use among children or pregnant women.

Dosage

Zinc gluconate, one table or lozenge containing 9–24 mg of elemental zinc, up to every 2 or 3 hours while awake, for the first few days of ARI illness.

Precautions

Zinc can inhibit the absorption of other minerals (copper) if used for extended periods of time. Nasal formulations have been associated with the loss of smell.

Among 13 trials of zinc including 1400 participants, approximately half reported positive and half reported negative results.

Mind Body

Placebo, Meaning, and Mind-Body Effects

During the past two decades I have read reports of hundreds of trials and dozens of systematic reviews and become increasingly convinced of the importance of mind-body effects, otherwise described as placebo or meaning effects.269, 270, 271, 272, 273 Positive thinking, suggestion, expectancy, and belief in the therapeutic value of a given remedy can be a powerful healing force. While regular exercise, balanced nutrition, and tobacco cessation are clearly associated with fewer and less severe illness episodes, so too are positive mental health attributes such as favorable psychological profile and healthful social relationships. Psychological predispositions, especially sociability and a positive emotional style, are predictive of both symptomatic and physiological outcomes. For the integrative clinician, this means that understanding an individual’s belief system may be a crucial part of the therapeutic encounter. If a patient already believes in a safe therapy, reinforcing that belief may enhance the therapeutic response. If patients are wary of a mentioned remedy, clinicians should not press the issue. Remember that reassurance, empathy, empowerment, and positive prognosis can all be usefully employed in the clinical encounter.

Pharmaceuticals and Conventional Cold Products

Antihistamines

Drugs blocking the effects of histamine have been sold as cold remedies for more than a century but, interestingly, have been subjected to less in terms of rigorous RCT research than alternatives such as vitamin C, zinc, and echinacea. Nevertheless, there is reasonable evidence of the modest benefit of first generation antihistamines, such as diphenhydramine, clemastine fumarate, and chlorpheniramine, in reducing nasal drainage.274, 275, 276, 277 However, effects appear to be more attributable to anticholinergic mechanisms than antihistamine effects, and second generation “nonsedating” antihistamines do not seem to provide benefit.²⁷⁸ For adults who do not mind the potential sedating or membrane-drying effects, or those with allergic responses, a first generation antihistamine may be a reasonable choice. For children, where there is no positive evidence whatsoever, antihistamines should be reserved for allergic rather than infectious rhinitis.

Decongestants

The oral decongestant, pseudoephedrine, has been tested in several clinical trials and appears to have minor benefit in reducing nasal congestion and drainage.279, 280, 281, 282 Side effects, including anxiety, dizziness, insomnia, and palpitations, are fairly common. More worrisome is the potential risk of elevated blood pressure and cardiac arrhythmia. Phenylpropanolamine, for decades a popular over-the-counter decongestant, was taken off the market after studies indicated an association with increased mortality, particularly among elderly individuals.²⁸³

The topical intranasal decongestant, oxymetazoline, has been shown to decrease nasal airway resistance as well as mucus production and drainage.284, 285, 286, 287 Intranasal phenylephrine has been less extensively studied but likely has similar effects. Unfortunately, these proven benefits come at the risk of nasal membrane dryness and discomfort. Oxymetazoline should be used for no more than 4 days as rebound nasal congestion can occur.

Cough Suppressants

Dextromethorphan, the active ingredient in cough remedies designated with “DM,” is widely used as an over-the-counter cough suppressant. Codeine, and to a lesser extent hydrocodone, are prescribed for cough and are thought to work through similar opioid-mediated mechanisms. As such, these medications have side effects including sedation, constipation, and, potentially, respiratory suppression. While most patients and clinicians agree that these remedies work, there is considerable debate over effect size and mechanism of action due to a lack of appropriate evidence.288, 289, 290 The best systematic review of cough remedies for children and adults concluded: “there is no good evidence for or against the effectiveness of OTC medicines in acute cough.”²⁹¹ Benzonatate (Tessalon perles) is licensed as a prescription antitussive but appears to have been given this indication despite a lack of good evidence.

Analgesics/Antipyretics

There is no doubt that acetaminophen and nonsteroidal antiinflammatories (NSAIDs), such as aspirin, ibuprofen, and naproxen, are effective in treating pain and fever that may accompany the common cold. However, some reports suggest that viral shedding may be prolonged by analgesics.292, 293 While limited use for pain reduction is eminently reasonable, the widespread use of NSAIDs for general common cold symptoms is not justified, as evidence-of-benefit is marginal, and many thousands of individuals die each year from NSAID-attributable gastrointestinal hemorrhage and congestive heart failure.294, 295, 296

Anticholinergics

Ipratropium nasal spray has been evaluated by several good quality RCTs regarding its efficacy in the amelioration of the symptoms of infectious and allergic rhinitis.297, 298 These trials, including a dose-response trial among 955 individuals with community-acquired common cold,²²⁸ reported definite benefit in terms of reduced nasal congestion and drainage. Common side effects include headache, uncomfortable nasal dryness, and nosebleed.

Combination Formulas

The multibillion-dollar market in cold remedies is dominated by numerous products containing combination formulas. Loopholes in FDA regulations have allowed pharmaceutical companies to mix various decongestants, antihistamines, analgesics, and antitussives, and then market these products under a variety of brand names and questionable claims. While there is some evidence of the effectiveness of these products from several RCTs,274, 299 very few if any of currently marketed products have been tested in large, well-controlled RCTs. Personally, I recommend against using any combination cold formula, with a possible exception for those who are convinced that a specific formula works for them. Perhaps most importantly, clinicians as well as parents should be made aware that no cold formula has ever been proven to work in children. In my opinion, acetaminophen (paracetamol) is the only currently justifiable treatment of pain in children.

Antivirals

Dozens of phase I and II trials using experimental rhinovirus infection models have reported benefit for several different antiviral drugs.300, 301, 302, 303, 304 None, however, have demonstrated safety or efficacy in the treatment of community-acquired colds and therefore none can currently be recommended. Nevertheless, this remains an active area of research; safe and effective antiviral cold treatments may become available in the future.

Conventional treatments, such as antihistamines, decongestants, and cough remedies, may help slightly with some symptoms but do tend to have side effects.

Prevention Prescription.

• •Do not smoke
• •Exercise regularly
• •Wash hands frequently
• •Eat a balanced nutritious diet, including foods containing vitamin C and zinc
• •Maintain supportive social relationships
• •Reduce exposure to people with colds
• •Reduce stressors and/or negative responses to stress
• •Antibiotics should not be used for the treatment of cold symptoms in children or adults.
• •There is some evidence for the effectiveness of andrographis (400 mg twice daily), vitamin C (200–500 mg daily), ginseng (100 mg daily), and probiotics in the prevention of colds. As the evidence is weak, consider these treatments only during high-risk times.

Therapeutic Review.

Below is a summary of therapeutic options for common cold. None are proven beyond reasonable doubt to be safe and effective. Nevertheless, these are all reasonable options given best current evidence of benefit and harm.

Treatment of Common Cold

Botanicals

• •Andrographis. Consistent preliminary evidence of benefit, no major concerns of harm. No good reason to pick one formulation or dose regimen over another. A common dose is 400 mg of dried herb, or extract containing 5 to 20 mg of andrographolide, up to three times daily for the first few days of illness.
• •Echinacea. Contradictory evidence, with several positive trials. Evidence on prevention is more consistent than that for treatment. No serious concerns of harm but should be avoided in pregnancy. Use three or four times daily for the first few days of a cold. No strong reason to pick one formulation over another
• •Pelargonium/Umckaloabo. Contradictory evidence, with a few positive trials. No serious concerns of harm. Use three or four times daily for the first few days of a cold. No strong reason to pick one product over another

Supplements

• •Vitamin C. Contradictory evidence, with several positive trials. Water-soluble vitamin. Necessary nutrient. Very safe in reasonable doses.
• •Zinc. Contradictory RCT evidence, with several positive trials, particularly with higher doses of zinc acetate. Use lozenges frequently for the first couple days of a cold. Side effects may include bad taste or nausea.
• •Astragalus, chamomile, garlic, ginger, ginseng, lemon, peppermint, hot baths, hot moist air, nasal saline, and chicken soup are all unproven but safe supportive therapies.

Pharmaceuticals

• •First generation (sedating) antihistamines may decrease nasal congestion but may cause drowsiness.
• •Intranasal decongestants appear to be effective in decreasing nasal congestion and drainage but quite often cause nasal dryness or irritation, and, rarely, insomnia, palpitations, or elevated blood pressure.
• •Oral decongestants may be effective in decreasing nasal congestion but may cause insomnia, palpitations, or elevated blood pressure.
• •Intranasal ipratropium appears to be effective in decreasing nasal congestion and drainage but may cause headache, nasal irritation, or nosebleed.
• •Antivirals for true influenza of no more than 36 hours duration may reduce symptom severity, duration, and infectivity

There is no good evidence of the effectiveness of any treatment, conventional or integrative, in children. While children can suffer side effects, they are less likely than adults to benefit from the placebo effect. Dr. Barrett says, “Don’t drug the kids!”

Key Web Resources

PubMed Health	http://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0024671/
Medline Plus	http://www.nlm.nih.gov/medlineplus/commoncold.html
American Academy of Family Medicine	http://www.aafp.org/afp/2012/0715/p153.html
Wikipedia	https://en.wikipedia.org/wiki/Common_cold