The common cold, also known as viral upper respiratory tract infections, is a self-limiting contagious condition characterized by upper respiratory tract congestion, watery nasal discharge, headache, cough, sore throat, watery eyes, and sneezing. Although there are more than 200 different types of viruses capable of infecting the upper respiratory tract, including coronavirus, adenovirus, and parainfluenza virus, it is the rhinovirus (rhin, derived from Greek, meaning "nose") that is responsible for causing approximately 30% to 50% of all colds.1 The optimum environment for the proliferation of rhinoviruses is temperature in the region of 91[degrees]F, the temperature within the nasal cavity.1 Although we are exposed to many cold viruses throughout the year, most adults experience 2 to 4 cold episodes on an annual basis whereas children on the average contract 6 to 10 colds in any given year.2,3 The differential in cold episodes between adults and children can be explained, in part, with the fact that adults have a more developed immune system against the various cold pathogens, or a greater host resistance. In the United States, the common cold is most prevalent during the fall and the winter seasons when the ambient air is lower in humidity. It is known that most cold-causing viruses survive and thrive in an environment that is low in humidity, which is characteristic of the colder months. In addition, when the mucous membranes that line the nasal cavities become dry, it creates a more hospitable situation for viral infection. Research also indicates that allergies that affect the nose and throat, as well as psychological stress, increase the incidence of cold viruses. Although external factors may contribute to creating more favorable conditions for "catching" a cold, the primary causative factor is a decrease in host resistance, or immune function. Therefore, the best means of protection against the common cold is through the maintenance of a healthy immune system.
An Echinacea purpurea extract is safe and effective for prevention of the common cold.
According to the National Institute of Allergy and Infectious Diseases, the estimated annual cost for the common cold in the United States is approximately $40 billion a year.4 Studies indicate that there are more than 1 billion cases of the common cold on a yearly basis, with an estimated loss of 189 million school days and 126 million workdays. Although the common cold is usually a mild, self-limiting condition, it accounted for more than 100 million visits to family practitioners annually, at an estimated cost of $20 billion per year due to cold-related work loss. It has been reported that more than 33% of patients who visited a physician received a prescription for antibiotics, an estimated 41 million prescriptions, with an expenditure of $1.1 billion each year, although antibiotics are known to be ineffective for treating viral infections, such as the common cold.5 The unnecessary prescription of antibiotics and its overuse has resulted in antimicrobial resistance, with health implications on a global level. According to the World Health Organization, "Inappropriate and irrational use of antimicrobial medicines provides favorable conditions for resistant microorganisms to emerge, spread and persist."5
The inappropriate use of antibiotics for treating the common cold has resulted in both individual and global health implications that far exceed the actual financial costs for treatment.5,6 In order for practitioners to provide best patient care for treating the common cold, clearly defined guidelines for prevention and a holistic, integrative treatment strategy that both supports immune function and helps alleviate associated cold symptoms should be the cornerstone for a well-balanced, effective treatment protocol. This article focuses on a proprietary phytomedicine extract derived from Echinacea purpurea (Echinaforce), which has demonstrated to be safe and effective as a prophylactic treatment of the common cold over a 4-month period.7
PHYTOMEDICINE PROFILE
Echinacea spp L. (Fam. Asteraceae) is often called purple coneflower due to its distinctive coloration and daisy-like floral structure. The floral arrangement is a composite of both ray and disk flowers, characterized by rich purple-to-pink elongated (ray flower) petals attached to the peripheral circumference of the flower head, which surround orange-brown florets (disk flowers) that are seated in a spiral arrangement on a centrally located cone-like structure.
Echinacea is a tall, hardy, perennial wildflower, indigenous to North America, and holds historical significance for its use as a medicinal plant by Native Americans. The root preparation of Echinacea was used internally for treating coughs, stomach upset, and easing the pain of sore throat and toothache. For external purposes, it was valued for treating wounds and snakebite and as a cure for rabies. Echinacea was introduced to Western medicine in the 1890s and was recommended for skin problems, respiratory tract infections, and sinus infections. Today, Echinacea is used primarily to reduce the symptoms and duration of colds, influenza, and upper respiratory tract infections and to help stimulate the activity of the immune system.
Phytochemistry
Echinacea is one of the well-studied herbal medicines today. Three species of Echinacea are used in phytomedicine products: Echinacea purpurea, Echinacea angustifolia, and Echinacea pallida. The constituents of Echinacea preparations vary, depending on the specific species and the part of the plant used.
Echinacea purpurea is one of the most important and well-known plants in the world. It is also the most widely cultivated medicinal plant species, which has been used as a preventive for infectious diseases in both upper and lower respiratory systems.8,9 The complex chemical composition of aerial and root parts of Echinacea purpurea involves caffeic acid derivatives (0.6%-2.1% roots), including cichoric acid (1.2%-3.1% flowers), alkamides (0.001%-0.4%), water-soluble polysaccharides (arabinoxylan and arabinogalactan), and flavonoids of quercetin and kaempferol (0.48%). The root of Echinacea purpurea differs in its constituents from the aerial plant parts by containing polyacetylene derivatives, polysaccharides (fructosans, arabinogalactans), and glycoproteins consisting of 3% protein.
Phytopharmacology
Immunostimulant activity
The immunostimulant activity of Echinacea purpurea is a result of its combined effect of several chemical constituents and is caused by 3 mechanisms: phagocytosis activation, fibroblast stimulation, and the enhancement of respiratory activity that results in augmentation of leukocyte mobility.10 There are several in vivo studies on the immunomodulatory and anti-inflammatory effects of Echinacea purpurea that indicate that innate immunity is enhanced through the administration of the plant actives and that the immune system is strengthened against pathogenic infections through activation of macrophages, neutrophils, polymorphonuclear leukocytes, and natural killer cells.11 Furthermore, research indicates that the pharmacologically active alkylamides are particularly involved in the immunomodulatory effect. The mechanism of action is known to occur when the alkylamides bind specifically to the CB2 receptor, an endocannabinoid receptor located on immune cells. This binding results in the modulation of the immune response through regulated TNF-[alpha] secretion, which regulates the activation of the immune system.12,13
RESEARCH IN REVIEW7
Jawad M, Schoop R, Suter A, Klein P, Eccles R. Safety and efficacy profile of Echinacea purpurea to prevent common cold episodes: a randomized, double-blind, placebo-controlled trial [published online ahead of print September 16, 2012]. Evid Based Complement Altern Med. doi:10.1155/2012/841315.
OBJECTIVE
The primary objective of this study was to evaluate the efficacy and safety parameters of Echinacea purpurea during long-term treatment. This study was designed to examine the efficacy profile with predefined, primary variables of efficacy and with a suitable sample size based on power calculations.7 This research study represented the largest trial to date to assess the safety and efficacy of Echinacea extract for the prevention of common cold episodes.
STUDY DESIGN
This study was a randomized, double-blind, parallel, placebo-controlled clinical trial that was conducted at the Common Cold Center in Cardiff University in the United Kingdom over a 4-month period. The study participants (N = 755) were healthy male and female adults (>=18 years of age), who experienced 2 or more colds per year, and met the inclusion criteria. Subjects were randomized to receive either Echinacea or placebo. At the initial intake visit, participants received either the test material or placebo medication for a 1-month period of treatment and a journal for documenting potential adverse side effects, incidence and severity of cold-related symptoms, and the use of any concurrent pharmaceutical medication. During each month's follow-up visit, participants returned unused treatment material, along with completed journal records to access compliance and were issued a new month's supply of treatment material and a new journal. In addition, subjects were provided with nasal swab kits for self-collection of nasal secretions for viral identification during acute cold episodes.
The test material used in the clinical trial was the commercially available Echinaforce drops (A. Vogel Echinaforce, http://www.Avogel.ca, Ghent, New York; A. Vogel Bioforce AG, Roggwil, Switzerland), a proprietary Echinacea purpurea alcoholic (57.3% m/m) extract prepared from freshly harvested leaves (95%) and roots (5%), standardized to contain 5 mg/100 g of the active constituent dodecatetraenoic acid isobutylamide. The placebo drops contained the same amount of alcohol and was similar in color, consistency, odor, and flavor as the test material.
Patients were randomly allocated to receive either the treatment group or the placebo group. The therapy regimen adhered to the manufacturer product recommendations. Participants administered 0.9 mL of the standardized Echinacea purpurea extract 3 times daily as the prevention for the common cold, which equated to 2400 mg of extract per day. During the acute stages of colds, participants were instructed to increase the dose by administering 0.9 mL of the extract 5 times per day, an equivalent of 4000 mg of extract. To achieve maximum local antiviral and anti-inflammatory effects, subjects were instructed to add each single dose in water and to retain the mixture in the mouth for the count of 10 seconds. The same method of administration was applied to the placebo group.
RESULTS
A total of 755 participants were included and randomized into either the Echinacea group or the placebo treatment group. Of these, 82 subjects discontinued the trial prematurely, with a remaining population of 673 test subjects who completed the study. There were no baseline differences between the treatment groups, with the exception that participants who were randomized to the Echinacea group were inadvertently more susceptible to colds, as measured by the number of colds previously experienced. The participants in the placebo group were significantly less susceptible to cold infections than those in the Echinacea test group (P < .05). There were a total of 293 adverse events that occurred with Echinacea and 306 with the placebo treatment. There were no severe adverse events observed with the Echinacea group; however, there was 1 severe adverse event involving glandular fever that occurred with a placebo group participant who required hospitalization. Approximately 64% of participants in the Echinacea group and 71% in the placebo group assessed the tolerability of the treatment to be "good" or "very good."
An analysis of the prophylactic efficacy was assessed concurrently with the safety variables during the long-term treatment with Echinacea (Echinaforce). In summary, the participants in the Echinacea group experienced 149 cold episodes, with a combined duration of 672 days, in comparison with those in the placebo group, who reported 188 colds lasting a combined total of 850 days. The total number of days with cold episodes was significantly fewer in the Echinacea group than in the placebo group (P < .05). In addition, those in the Echinacea group experienced fewer recurring colds (65 cold episodes in 28 participants) than those in the placebo treatment (100 episodes in 43 subjects), reaching a statistical significance (P < .05). Furthermore, a significant factor in this study was the use of concurrent medications as an additional treatment option for cold symptoms. In the placebo group, significantly more colds were treated additionally with aspirin or ibuprofen (+52%) than among those participants with colds taking Echinacea.
Of the total number of nasal secretion samples collected in the study (n = 201), the presence of a respiratory virus was confirmed in 128 samples. Throughout the entire course of the study, 54 viral infections were identified in the Echinacea group and 74 in the placebo group. Interestingly, the most potent effect was observed with the membranous viruses, such as coronavirus, parainfluenza virus, and influenza virus, with 24 infections detected in the Echinacea group and 47 identified in the placebo group. In those patients who adhered 100% to the study medication for the entire 4-month duration of the study, 36 colds with a combined duration of 155 days were reported from the Echinacea test groups (n = 88) in comparison with 58 colds in 268 days that were recorded in the placebo group (n = 99; P < .0001). This equates to a 58% difference in the number of cold episode days.
SUMMARY
The research study in this review represents the largest clinical trial to date that evaluated the safety and efficacy of Echinacea purpurea for prophylactic treatment of the common cold, in addition to investigating its risk-benefit in a long-term treatment period. The clinical application of the proprietary-standardized Echinacea purpurea extract (Echinaforce) demonstrated efficacy as a preventive cold treatment option over a 4-month duration. This study showed that Echinacea's long-term prevention was associated with a reduction in the total number of cold episodes, a reduction in the number of days with colds, and a reduction in cold episodes requiring additional medication. Furthermore, the Echinacea test agent inhibited virally confirmed colds, exhibited maximal effects on recurrent infections, and demonstrated that its preventive effects increased relative to therapy compliance and adherence to the protocol. In summary, Echinacea purpurea when taken as recommended for the prevention of the common cold appears to provide a positive risk to benefit ratio.7
REFERENCES