Trauma1's common cold facts/treatments/studies.
- 09-12-2007, 11:36 PM
Trauma1's common cold facts/treatments/studies.
Here's a quick guide to kicking a cold in the a$$ early:
Now there are something like 250 different common cold viruses known as "rhino viruses" which are responsible for roughly 50% of upper respiratory infections. As we are exposed to these different "rhino viruses," our body develops antibodies that will usually prevent future infection from the same strain. I would get into the viral mechanism of action, but i'll just say that antibiotics don't work against viral infections as their pathophysiology of infection is quite different than bacterial. Now with the common cold basically these "rhinoviruses" invade the cells in your nasal mucosa and begin viral replication. It's about this time that you become symptomatic (runny nose, headache, sneezing, sore throat, cough, or congestion) as a viral host cell dies, it releases more viral replications into the surrounding nasal mucosa tissue.
The Organs of Immunity:
There are five "immune" organs in the human body:
-The thymus gland is involved in the formation of T-cells.
-The tonsils and adenoids distinguish invaders that may need destroying.
-The spleen is the organ that filters blood and distributes T-cells and B-cells.
-The lymph glands form and store white blood cells.
-The bone marrow is where B-cells are produced.
What the Immune System Does:
The immune system is the body's defense against infectious organisms and other invaders. Through a series of steps called the immune response, the immune system attacks organisms and substances that invade our systems and cause disease. The immune system is made up of a network of cells, tissues, and organs that work together to protect the body.
The cells that are part of this defense system are white blood cells, or leukocytes. They come in two basic types (more on these below), which combine to seek out and destroy the organisms or substances that cause disease.
Leukocytes are produced or stored in many locations throughout the body, including the thymus, spleen, and bone marrow. For this reason, they are called the lymphoid organs. There are also clumps of lymphoid tissue throughout the body, primarily in the form of lymph nodes, that house the leukocytes.
The leukocytes circulate through the body between the organs and nodes by means of the lymphatic vessels. Leukocytes can also circulate through the blood vessels. In this way, the immune system works in a coordinated manner to monitor the body for germs or substances that might cause problems.
The two basic types of leukocytes are:
Phagocytes: cells that locate and chew up invading organisms by a process called phagocytosis.
Lymphocytes: cells that allow the body to remember and recognize previous invaders and help the body destroy them when and if encountered at a different time.
A number of different cells are considered phagocytes. The most common type is the neutrophil, which primarily fights bacteria. If doctors are worried about a bacterial infection, they might order a blood test to see if a patient has an increased number of neutrophils triggered by the infection. Other types of phagocytes have their own jobs to make sure that the body responds appropriately to a specific type of invader.
There are two kinds of lymphocytes: The B lymphocytes(Humoral immunity) and the T lymphocytes(Cell-mediated immunity):
Lymphocytes start out in the bone marrow and either stay there and mature into B type lymphocytes, or they leave for the thymus gland where they mature into T type lymphocytes. B lymphocytes and T lymphocytes have separate jobs to do: B lymphocytes are like the body's military intelligence system, seeking out their targets and sending defenses to lock onto them. T cells are like the soldiers, destroying the invaders that the intelligence system has identified. Here's how it works.
Antigens are foreign substances that invade the body. When an antigen is detected, several types of cells work together to recognize and respond to it. These cells trigger the B lymphocytes to produce antibodies, specialized proteins that lock onto specific antigens. Antibodies and antigens fit together like a key and a lock.
Once the B lymphocytes have produced antibodies, these antibodies continue to exist in a person's body, so that if the same antigen is presented to the immune system again, the antibodies are already there to do their job. That's why if someone gets sick with a certain disease, like chickenpox, that person typically doesn't get sick from it again. This is also why we use immunizations to prevent getting certain diseases. The immunization introduces the body to the antigen in a way that doesn't make a person sick, but it does allow the body to produce antibodies that will then protect that person from future attack by the germ or substance that produces that particular disease.
Although antibodies can recognize an antigen and lock onto it, they are not capable of destroying it without help. That is the job of the T cells. The T cells are part of the system that destroys antigens that have been tagged by antibodies or cells that have been infected or somehow changed. (There are actually T cells that are called "killer cells.") T cells are also involved in helping signal other cells (like phagocytes) to do their jobs.
Antibodies can also neutralize toxins (poisonous or damaging substances) produced by different organisms. Lastly, antibodies can activate a group of proteins called complement that are also part of the immune system. Complement assists in killing bacteria, viruses, or infected cells.
All of these specialized cells and parts of the immune system offer the body protection against disease. This protection is called immunity.
Humans have three types of immunity — Innate, Adaptive, and Passive:
Everyone is born with innate (or natural) immunity, a type of general protection that humans have. Many of the germs that affect other species don't harm us. For example, the viruses that cause leukemia in cats or distemper in dogs don't affect humans. Innate immunity works both ways because some viruses that make humans ill — such as the virus that causes HIV/AIDS — don't make cats or dogs sick either.
Innate immunity also includes the external barriers of the body, like the skin and mucous membranes (like those that line the nose, throat, and gastrointestinal tract), which are our first line of defense in preventing diseases from entering the body. If this outer defensive wall is broken (like if you get a cut), the skin attempts to heal the break quickly and special immune cells on the skin attack invading germs.
We also have a second kind of protection called adaptive (or active) immunity. This type of immunity develops throughout our lives. Adaptive immunity involves the lymphocytes (as in the process described above) and develops as children and adults are exposed to diseases or immunized against diseases through vaccination.
Passive immunity is "borrowed" from another source and it lasts for a short time. For example, antibodies in a mother's breast milk provide an infant with temporary immunity to diseases that the mother has been exposed to. This can help protect the infant against infection during the early years of childhood.
Everyone's immune system is different. Some people never seem to get infections, whereas others seem to be sick all the time. As people get older, they usually become immune to more germs as the immune system comes into contact with more and more of them. That's why adults and teens tend to get fewer colds than kids — their bodies have learned to recognize and immediately attack many of the viruses that cause colds.
The key is you want to hit a cold right when your symptoms start. Now i will tell you all that there is NO CURE for the common cold at this time. The treatment is typically designed to help alleviate associated symptoms that are usually self limiting. Most theories in cold remedies aim at boosting the immune systems response early on in the cold virus replication cycle to shorten it's overall duration/severity of infection.
Pharmacological/Nutritional Intervention For Colds:
-Vitamin C: (500mg 4x/daily) slightly reduces severity and duration of cold symptoms, however many studies have been inconclusive. It is recommended to begin dosing vitamin c as suggested here at the very onset of symptoms.
-Zinc Gluconate: (preferably lozenge or nasal spray form/route as studies seem to support this delivery method better due to more adequate distrubution in infected nasal mucosa tissues to illicit benefits.) While zinc's mechanism of action in cold prevention is unclear, it has shown to have immune boosting/anti-viral properties. Taken as a lozenge, zinc releases ions that prevent the common cold virus from maturing and attaching to airways. Choose zinc gluconate or zinc acetate without flavoring agents such as citric and tartaric acids—they appear to stunt its preventive powers. Take it only once or twice a day for a week at a time.
-Oral Hydration: is important to maintain the bodies state of homeostasis while preventing dehydration brought on by fever. It also assists in keeping mucous accumulation thin for better expectoration.
-Antihistamines: (benadryl,claritin,vistaril,al legra,zyrtec,doxyalamine succinate) These pharmacologic medications help to dry up (rhinorhea) runny nose/secretion symptoms. Some antihistamine class medications are known to also cause drowsiness (usually dose dependant) in many individuals. Benadryl being the most common due to being an OTC medication.
-Antipyretics: (tylenol,motrin,naprosyn,aspir in).....keeping a fever under control will help alleviate some symptoms. A fever however is the bodies natural defense response to foreign antigen invasion which helps to suppress viral/bacterial replication. It also provides an environment suitable for rapid white blood cell proliferation to combat the foreign invasion.
-Cough suppressants: (*codeine:by far the best at cough suppression due to direct effects on the cerebral medulla cough mechanism, dextromethorphan) helps suppress the cough reflex.
-Expectorants: (humibid,mucinex) keeps bronchial/nasal mucous accumulation thin for better expectoration.
-Calorie Intake: During a state of infection your body uses extra calories to carry out disease fighting processes....make sure you give the body what it needs to do its job!
-Decongestants:(Psuedoephedrine,Phenylephrine/neosynephrine) A decongestant is a broad class of medications used to relieve nasal congestion. Generally, they work by reducing swelling of the mucous membranes in the nasal passages by way of vasoconstriction.
-Probiotics: (Lactobacillus Casei Ke-99 AKA: RPN'S GUT HEATLH) They exhibit probiotic effects(positive effects on the host) and protect against pathogenic bacteria by means of competitive exclusion (i.e., by competing for growth and limiting pathogenic bacteria within the intestinal tract.) There is evidence to suggest that this probiotic process may improve immune function by increasing the number of IgA-producing plasma cells, increasing or improving phagocytosis as well as increasing the proportion of T lymphocytes and Natural Killer cells.
There are many other cold remedies which aim at alleviating cold symptoms, however many of them show unproven results in clinical testing thus i have not listed some of them.
I have many interesting studies that i shall post in this thread and shall keep this as an ongoing work in progress in addition to a learning experience for all.
Last edited by Trauma1; 12-23-2008 at 05:53 PM.
Evolutionary Muse - Inspire to Evolve
- 09-12-2007, 11:40 PM
Treatment of the Common Cold - MADELINE SIMASEK, M.D., and DAVID A. BLANDINO, M.D.University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
Acute upper respiratory infection is the second most common diag-nosis in physician offices1and the most common discharge diagno-sis in emergency departments.2A survey revealed that almost one fourth of U.S. adults had taken a cough or cold medication with or without a sedating antihistamine in the pre-ceding week.3Prevention of colds and influ-enza and “immune boosting” were among the top 10 reasons participants took vitamins and herbal supplements.3A survey conducted by the Centers for Disease Control and Pre-vention showed that, in 1991, two thirds of three-year-olds had taken cough or cold medicine in the preceding 30 days.4Because colds are common presentations in physi-cian offices, and cough and cold remedies are used almost universally, it is important that physicians know the evidence (Table 15-9andTable 25,6,10) that supports or refutes the use of these medications.11The literature on the common cold isextensive, but it is inconsistent in its rigor.Among the numerous studies, the clinicaldefinition often is unclear or variable, natu-ral and experimental colds are evaluated, and age ranges are sometimes broad and variable. Furthermore, the number of par-ticipants often is small, interventions varyfromindividualtocombinatio nmedications,compliance often is not addressed, single ormultiple symptom outcomes are used, and outcomes are subjectively reported in somestudies and objectively reported in others. Not surprisingly, there is great heterogeneity among the results. These limitations in the literature limit the ability to make confident and specific recommendations about treat-ments. For clinical purposes, the literature on traditional pharmacologic treatment isbest summarized by making separate rec-ommendations for cough alone and for con-gestion and rhinorrhea. For complementary and nonpharmacologic treatments, the lit-erature addresses more global outcomes.
Epidemiology and Clinical Presentation:
The common cold is caused by various respi-ratory viruses, most commonly a rhinovirus. The common cold is a viral illness that affects persons of all ages, prompting frequent use ofover-the-counter and prescription medications and alternative remedies. Treatment focuseson relieving symptoms (e.g., cough, nasal congestion, rhinorrhea). Dextromethorphan may bebeneficial in adults with cough, but its effectiveness has not been demonstrated in children andadolescents. Codeine has not been shown to effectively treat cough caused by the common cold.Although hydrocodone is widely used and has been shown to effectively treat cough caused byother conditions, the drug has not been studied in patients with colds. Topical (intranasal) andoral nasal decongestants have been shown to relieve nasal symptoms and can be used in adoles-cents and adults for up to three days.Antihistamines and combination antihistamine/deconges-tant therapies can modestly improve symptoms in adults;however,the benefits must be weighedagainst potential side effects. Newer nonsedating antihistamines are ineffective against cough.Topical ipratropium, a prescription anticholinergic, relieves nasal symptoms in older childrenand adults. Antibiotics have not been shown to improve symptoms or shorten illness duration.Complementary and alternative therapies (i.e., Echinacea, vitamin C, and zinc) are not recom-mended for treating common cold symptoms; however, humidified air and fluid intake maybe useful without adverse side effects. Vitamin C prophylaxis may modestly reduce the dura-tion and severity of the common cold in the general population and may reduce the incidenceof the illness in persons exposed to physical and environmental stresses. (Am Fam Physician2007;75:515-20, 522. Copyright © 2007 American Academy of Family Physicians.)Patient information:A handout on the com-mon cold, written by the authors of this article, isprovided on page 522.See related editorialon page 476.Downloaded from the American Family Physician Web site at American Family Physician -- American Academy of Family Physicians. Copyright © 2007 American Academy of Family Physicians. For the private, noncommercialuse of one individual user of the Web site. All other rights reserved. Contact firstname.lastname@example.org for copyright questions and/or permission requests.
516American Family Physicianwww.aafp.org/afpVolume 75, Number 4 February 15, 2007
The Common Cold:
Adults have an average of two to four episodes annually, and young children may have as many as six to eight episodes. A common cold is characterized by sore throat, malaise, and low-grade fever at onset. These symptoms resolve within a few days and are followed by nasal con-gestion, rhinorrhea, and cough within 24 to 48 hours after onset of the first symptoms. The second set of symp-toms are what prompt most patients to see a physician for relief.1Symptoms usually peak around day 3 or 4 and begin to resolve by day 7.12Nasal discharge, appearing at the peak of illness, can become thick and purulent and may be misdiagnosed as a bacterial sinus infection.13Traditional Pharmacologic TherapyBecause there are no effective antivirals to cure the common cold and few effective measures to prevent it, treatment should focus on symptom relief. The most commonly used treatments include over-the-counter antihistamines, decongestants, cough suppressants, and expectorants. These treatments can be used alone or in combination.Although a cold is a viral illness, antibiotics often are inappropriately prescribed to patients, even when bacte-rial complications (e.g., pneumonia, bacterial sinusitis)are not present. Studies of antibiotics for the treatment of the common cold focus on cure rate, symptom persis-tence, prevention of secondary bacterial complications,and adverse effects. Systematic reviews have shown that antibiotics have no role in the treatment of the common cold. This is because antibiotics are ineffective at reducing symptom duration or severity and because of the risk of adverse gastrointestinal effects,cost of treatment, and increased resistance of bacteria toantibiotics.
Cochrane review showed that there is a lack of good evidence to determine the effectiveness of any over-the-counter product at reducing the frequency or severity of cough in children or adults.5Some authors explicitly recommend against the use of these medications.16,17The American College of Chest Physicians guideline does not recommend centrally acting cough suppres-sants (e.g., codeine [Robitussin AC], dextromethorphan [Delsym]) for cough secondary to upper respiratory tract infection.18Despite these conclusions, two of the three studies included in the Cochrane review suggest that dextro-methorphan provides a modest clinical benefit.5,19Oneof these studies (a meta-analysis) showed a reduction inthe frequency and severity of cough for persons 18 years or older without significant adverse effects.19The aver-age treatment difference was 12 to 17 percent in favor ofdextromethorphan for cough bouts, cough components, and cough effort.19One study included in the Cochrane review showedSORT: KEY
RECOMMENDATIONS FOR PRACTICE:
Clinical recommendation Evidencerating References Antibiotics are not recommended for treatment of the common cold in children or adults.A14, 15Dextromethorphan (Delsym) is a treatment option for adults with cough caused by the common cold.B5, 19Topical (intranasal) or oral nasal decongestants, used for up to three days, is a treatment option foradolescents and adults.B7, 8, 30Topical ipratropium (Atrovent) is a treatment option for nasal congestion in children older than sixyears and in adults, although it is expensive.B9Codeine (Robitussin AC) and other narcotics, dextromethorphan (Delsym), antihistamines, andcombination antihistamine/decongestants are not recommended to treat cough or other coldsymptoms in children.B5-7, 10, 17Older first-generation antihistamines and combination antihistamine/decongestants are treatment options for cough and cold symptoms in adults if the benefits outweigh the adverse effects.B6Among available complementary treatments, vitamin C prophylaxis may decrease the severity and duration of cold symptoms; however, vitamin C, zinc, and Echinacea are not recommended for active treatment.B31-34, 36A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, see page 453 orhttp://www.aafp.org/afpsort.xml.
that combination antihistamine/decongestant medi-cations have a modest benefit but with significantly increased adverse effects. In contrast, newer-generation,nonsedating antihistamines do not effectively reducecough.18Because of the conflicting evidence, physiciansmust weigh the risks and benefits of dextromethorphanor combination antihistamine/decongestant medica-tions (Table 311,20).No medication available in the United States has beenshown to effectively treat cough in children.5,10Althoughclinical trials have reported a low incidence of minor adverse effects, anecdotal reports of serious adverse effects and dosing errors have prompted the AmericanAcademy of Pediatrics and other experts to caution against the use of these preparations in children.21-24There also is little evidence to support the use ofcodeine and its derivative hydrocodone (Hycodan) to relieve cough caused by the common cold in adults and children.5One small study of codeine use in children25and two small studies in adults26,27failed to show abenefit. Hydrocodone commonly is prescribed for sup-pression of cold-related acute cough. There are no stud-ies of hydrocodone use in patients withthe common cold, although the drug’seffectiveness has been demonstrated inpatients with other conditions.28,29
NASAL CONGESTION AND RHINORRHEA:
Several mechanisms can cause cold-related nasal congestion and rhinorrhea.12Although these mechanisms differ from those that cause allergy-related symptoms, antihistamines remain a popular therapy for the common cold. Although some randomized controlledtrials (RCTs) of older first-generationantihistamines have shown positiveresults for certain end points, a Cochrane review concluded that antihistaminesdo not alleviate cold-related sneezing ornasal symptoms to a clinically signifi-cant degree and do not affect subjective improvement in children or adults.6Evenif a slight clinical benefit exists, there are risks and adverse effects, especially withfirst-generation antihistamines.11There-fore, antihistamine monotherapy is not recommended for children and should beused cautiously in adults.Although a first-generation oral anti-histamine and decongestant combination may have some effect on nasal obstruc-tion, rhinorrhea, and sneezing in adoles-cents and adults, studies generally are ofpoor quality, and effects are small and may not be clinically significant. Antihis-tamine/decongestant treatment has not been shown to benefit young children.6Two systematic reviews have examinedthe use of nasal decongestants.7,30Thereviews included four trials that stud-ied the short-term benefits of a single-TABLE 1Overview of the Evidence for Cold Therapies in AdultsTherapyStudy findingsCough (one Cochrane review [17 studies])5Antihistamine/decongestant combinationTwo studies: one showed benefit withunfavorable side effects; one showed nobenefitAntihistaminesThree studies: no benefitCodeine (Robitussin AC)Two studies: no benefitDextromethorphan (Delsym)Three studies: two showed benefit; oneshowed no benefitDextromethorphan plussalbutamol* One study: limited benefit with unfavorable side effectsGuaifenesin (Mucinex)Two studies: one showed benefit; one showed no benefitMoguisteine*One study: very limited benefitMucolytic (e.g., Bisolvonlinctus*)One study: benefitCongestion and rhinorrhea (two Cochrane reviews [30 studies])6,7;two RCTs8,9)Antihistamine/decongestant combinationSeven studies: five showed some benefit fornasal obstruction; two showed no benefitSix studies: five showed some benefit forrhinorrhea; one showed no benefitAntihistaminesFive studies: no benefit for nasal obstruction Seven studies: benefit for rhinorrhea (first-generation antihistamines only)Intranasal ipratropium(Atrovent)One study: benefitOral or topical decongestants(single dose)Four studies: benefit for nasal obstructionOral decongestants (repeated doses)Two studies: one showed benefit for nasal obstruction; one showed no benefitRCT = randomized controlled trial.*—Not available in the United States.Information from references 5 through 9.The Common ColdFebruary 15, 2007 Volume 75, Number 4www.aafp.org/afpAmerican Family Physician517
518American Family Physicianwww.aafp.org/afpVolume 75, Number 4 February 15, 2007The Common Colddose topical (intranasal) or oral decongestant and one trial that studied the effects of repeated dosing. The single-dose decongestant had a moderate short-termbenefit for adolescents and adults with nasal conges-tion. Although a repeated dose of oral pseudoephedrine(Sudafed) over five days had no benefit,7,30another clini-cal trial showed that a 60-mg dose repeated four times a day over three days improved nasal airway resistanceand subjective scores in adults.8Given these findings, the use of topical or oral decongestants for a few days isreasonable and consistent with standard practice. Stud-ies of single-ingredient decongestants have not includedchildren younger than 12 years, and there have beenanecdotal reports of serious toxicity in young childrenusing oral decongestants.23Finally, a recent study supports the use of topical ipratropium (Atrovent) for rhinorrhea caused by peren-nial rhinitis and the common cold.9However, it isexpensive, requires a prescription, and is approved only for children older than six years.Complementary and Alternative TherapiesNontraditional complementary and alternative therapies used for the common cold include Echinacea, vitamin C, zinc, and humidified air and fluid intake.
Cochrane review concluded that, despite some studies that showed benefit, there is no solid evidence that Echinacea products effec-tively treat or prevent the common cold.31The review cited concerns about publication bias (i.e., positive studies were more likely to be published), poor study quality, and vari-ability of study results.31Two well-conducted studies showed no benefit from Echinacea angustifolia root32orthe aerial portion of Echinacea purpurea.33Because three species are available for medi-cal use, plant parts used and extractionmethods differ, and some preparationscontain additional ingredients, it is dif-ficult to make specific product or dosage recommendations.
Cochrane review showed that taking 200 mg or more of vitamin C daily does not significantly decrease symptom severity or duration when initiated after the onset of cold symptoms.34Data regarding prophylactic use of vitamin C are more varied. Thirty trials involving 9,676 cold episodes showeda statistically significant decrease in illness duration withvitamin C taken before onset of symptoms: an 8 percent decrease (95% confidence interval [CI], 3 to 13 percent)in adults and a 13.5 percent decrease (95% CI, 5 to 21percent) in children.34Likewise, 15 trials involving 7,045cold episodes demonstrated a decrease in severity scores and in days confined to the home.34Vitamin C did not decrease the incidence of cold in the general population. However, a subgroup of six trials involving runners, skiers, and soldiers participating in subarctic exercisesdemonstrated a 50 percent relative reduction in the riskof developing a cold (95% CI, 32 to 62 percent).34ZINCThe use of zinc has been shown to inhibit viral growth, and an RCT suggested that zinc could reduce the dura-tion of cold symptoms.35However, this has not been substantiated in subsequent RCTs.36Specifically, four of eight subsequent trials showed no benefit, and the other four may have been biased by the patients’ ability to recognize the adverse effects of zinc.36Because of these inconsistent study results, zinc cannot be recommended.TABLE 2Overview of the Evidence for Cold Therapies in ChildrenTherapyStudy findingsCough (Cochrane review [seven studies])5; one RCT10AntihistaminesTwo studies: no benefitAntihistamine/decongestant combinationTwo studies: no benefitCodeine plus guaifenesin (Robitussin AC)One study: no benefitDextromethorphan (Delsym)Two studies: no benefitDextromethorphan plus guaifenesin (Robitussin DM)One study: no benefitDextromethorphan plus salbutamol*One study: no benefitMucolytic (e.g., Letosteine*)One study: benefitOther combinationsOne study: no benefitCongestion and rhinorrhea (Cochrane reviews [four studies]6)AntihistaminesTwo studies (one using astemizole†): benefitAntihistamine/decongestant combinationTwo studies: no benefitDecongestantsNo studiesRCT = randomized controlled trial.*—Not available in the United States.†—Withdrawn from U.S. market in 1999.Information from references 5, 6, and 10.
Last edited by Trauma1; 12-23-2008 at 05:43 PM.
Evolutionary Muse - Inspire to Evolve
- 09-12-2007, 11:41 PM
February 15, 2007 Volume 75, Number 4www.aafp.org/afpAmerican Family Physician519
The Common Cold - HUMIDIFIED AIR AND FLUID INTAKE:
Studies of Rhinotherm (an apparatus that delivershumidified air at a controlled temperature of about 104 to 116.6°F [40 to 47°C]) have had conflicting results despite using similar equipment and methodology.37Because of these inconsistent results and the lack of uni-versal access to this equipment, Rhinotherm cannot be recommended. However, except for the theoretical risks associated with fluid intake,38humidified air and fluid intake are considered benign and possibly beneficial for the relief of common cold symptoms.11DATA SOURCES:For this article, the authors searched the Cochrane Database of Systematic Reviews, Medline (1996 to 2005), the Cochrane Registryof Clinical Trials (2003 to 2005), BMJ’s Clinical Evidence Concise, theNational Guidelines Clearinghouse, the Institute for Clinical SystemsImprovement, the Database of Abstracts of Reviews of Effectiveness,and EMBASE (2001 to 2005). The search was limited to English-languagesystematic reviews and randomized controlled trials, and recommenda-tions were limited to products available in the United States.Members of various family medicine departments develop articles for“Clinical Pharmacology.” This is one in a series coordinated by Allen F.Shaughnessy, Pharm.D., and Andrea E. Gordon, M.D., Tufts UniversityFamily Medicine Residency, Malden, Mass.The AuthorsMADELINE SIMASEK, M.D., is assistant program director of the Universityof Pittsburgh (Pa.) Medical Center (UPMC) and is clinical associate pro-fessor of pediatrics at the University of Pittsburgh School of Medicine.Dr. Simasek received her medical degree from Temple University,Philadelphia, Pa., and completed a pediatrics residency at Children’sHospital of Pittsburgh.DAVID A. BLANDINO, M.D., is chairman of the Department of Family and Community Medicine at UPMC Shadyside Hospital and is clinical associateprofessor of family medicine at the University of Pittsburgh School ofMedicine. Dr. Blandino received his medical degree from the University ofPittsburgh School of Medicine and completed a family medicine residency at Williamsport (Pa.) Hospital and Medical Center.Address correspondence to David A. Blandino, M.D., 5230 Centre Ave., Pittsburgh, PA 15232. Reprints are not available from the authors.Author disclosure: Nothing to disclose.REFERENCES1. Woodwell DA, Cherry DK. National ambulatory medical care survey:2002 summary. Adv Data 2004;346:1-44.2. McCaig LF, Burt CW. National hospital ambulatory medical care survey: 2002 emergency department summary. Adv Data 2004;340:1-34.3. Kaufman DW, Kelly JP, Rosenberg L, Anderson TE, Mitchell AA. Recent patterns of medication use in the ambulatory adult population of theUnited States: the Slone survey. JAMA 2002;287:337-44.4. Kogan MD, Pappas G, Yu SM, Kotelchuck M. Over-the-counter medica-tion use among US preschool-age children. JAMA 1994;272:1025-30.5. Schroeder K, Fahey T. Over-the-counter medications for acute cough inchildren and adults in ambulatory settings. Cochrane Database Syst Rev2004;(4):CD001831.6. Sutter AI, Lemiengre M, Campbell H, Mackinnon HF. Antihistamines for the common cold. Cochrane Database Syst Rev 2003;(3):CD001267.7. Taverner D, Latte J, Draper M. Nasal decongestants for the commoncold. Cochrane Database Syst Rev 2004;(3):CD001953.8. Eccles R, Jawad MS, Jawad SS, Angello JT, Druce HM. Efficacy andsafety of single and multiple doses of pseudoephedrine in the treat-ment of nasal congestion associated with common cold. Am J Rhinol2005;19:25-31.9. Hayden FG, Diamond L, Wood PB, Korts DC, Wecker MT. Effective-ness and safety of intranasal ipratropium bromide in common colds.A randomized, double-blind, placebo-controlled trial. Ann Intern Med 1996;125:89-97.10. Paul IM, Yoder KE, Crowell KR, Shaffer ML, McMillan HS, Carlson LC, etal. Effect of dextromethorphan, diphenhydramine, and placebo on noc-turnal cough and sleep quality for coughing children and their parents.Pediatrics 2004;114:E85-90. Accessed July 25, 2006, at: http://pediat-rics.aappublications.o...l/114/1/e85.11. Montauk SL. Appropriate use of common OTC analgesics and coughand cold medications. Leawood, Kan.: American Academy of FamilyPhysicians, 2002. Accessed July 24, 2006, at: http://www.aafp.org/afp/otcmonograph/index.html.12. Heikkinen T, Jarvinen A. The common cold. Lancet 2003;361:51-9.13. American Academy of Pediatrics. Subcommittee on Management ofSinusitis and Committee on Quality Improvement. Clinical practiceguideline: management of sinusitis [Published corrections appear inPediatrics 2001;108:A24, Pediatrics 2002;109:40]. Pediatrics 2001;108:798-808.14. Arroll B, Kenealy T. Antibiotics for the common cold and acute purulentrhinitis. Cochrane Database Syst Rev 2005;(3):CD000247.15. Fahey T, Stocks N, Thomas T. Systematic review of the treatment ofupper respiratory tract infection. Arch Dis Child 1998;79:225-30.16. Schroeder K, Fahey T. Systematic review of randomised controlled trials of over the counter cough medicines for acute cough in adults. BMJ 2002;324:329-31.17. Schroeder K, Fahey T. Should we advise parents to administer overthe counter cough medicines for acute cough? Systematic review of randomised controlled trials. Arch Dis Child 2002;86:170-5.18. Irwin RS, Baumann MH, Bolser DC, Boulet LP, Braman SS, Bright-ling CE, et al. American College of Chest Physicians. Diagnosis andTABLE 3Adverse Effects Associated with Cold TherapiesTherapyAdverse effectsAntihistaminesArrhythmi a, blurred vision, dizziness,dry mouth, hallucinations, heartblock, paradoxic excitability,respiratory depression, sedation,tachycardia, urinary retentionDecongestantsOral: agitation, anorexia,dysrhythmia, dystonic reactions,headache, hypertension, irritability,nausea, palpitations, seizure,sleeplessness, tachycardia, vomitingTopical: drying of nasal membranes, nosebleeds, rebound nasal congestionDextromethorphan(Del sym)Confusion, excitability, gastrointestinal disturbances,irritability, nervousness, sedationNOTE:Adverse effects may be more significant in young children and older adults.Information from references 11 and 20.
520 American Family Physicianwww.aafp.org/afpVolume 75, Number 4 February 15, 2007The Common Coldmanagement of cough executive summary: ACCP evidence-based clini-cal practice guidelines. Chest 2006;129(1 suppl);1S-23S.19. Pavesi L, Subburaj S, Porter-Shaw K. Application and validation of acomputerized cough acquisition system for objective monitoring ofacute cough: a meta-analysis. Chest 2001;120:1121-8.20. Kelly LF. Pediatric cough and cold preparations. Pediatr Rev 2004;25:115-23.21. Gadomski A. Rational use of over-the-counter medications in youngchildren. JAMA 1994;272:1063-4.22. Gadomski A, Horton L. The need for rational therapeutics in the use ofcough and cold medicine in infants. Pediatrics 1992;89(4 pt 2):774-6.23. Gunn VL, Taha SH, Liebelt EL, Serwint JR. Toxicity of over-the-countercough and cold medications. Pediatrics 2001;108:E52. Accessed July 25,2006, at: http://pediatrics.aappublications.or...l/108/3/e52.24. American Academy of Pediatrics. Committee on Drugs. Use of codeine-and dextromethorphan-containing cough remedies in children. Pediat-rics 1997;99:918-20.25. Taylor JA, Novack AH, Almquist JR, Rogers JE. Efficacy of cough sup-pressants in children. J Pediatr 1993;122(5 pt 1):799-802.26. Eccles R, Morris S, Jawad M. Lack of effect of codeine in the treatmentof cough associated with acute upper respiratory tract infection. J ClinPharm Ther 1992;17:175-80.27. Freestone C, Eccles R. Assessment of the antitussive efficacy of codeine in cough associated with common cold. J Pharm Pharmacol 1997;49:1045-9.28. Homsi J, Walsh D, Nelson KA, Sarhill N, Rybicki L, Legrand SB, et al. Aphase II study of hydrocodone for cough in advanced cancer. Am J HospPalliat Care 2002;19:49-56.29. Stolz D, Chhajed PN, Leuppi JD, Brutsche M, Pflimlin E, Tamm M. Coughsuppression during flexible bronchoscopy using combined sedationwith midazolam and hydrocodone: a randomised, double blind, pla-cebo controlled trial. Thorax 2004;59:773-6.30. Del Mar C, Glasziou P. Upper respiratory tract infection. Clin Evid2003;10:1747-56.31. Linde K, Barrett B, Wölkart K, Bauer R, Melchart D. Echinacea for pre-venting and treating the common cold. Cochrane Database Syst Rev2006;(1):CD000530.32. Turner RB, Bauer R, Woelkart K, Hulsey TC, Gangemi JD. An evaluation of Echinacea angustifolia in experimental rhinovirus infections. N Engl JMed 2005;353:341-8.33. Yale SH, Liu K. Echinacea purpurea therapy for the treatment of thecommon cold: a randomized, double-blind, placebo-controlled clinicaltrial. Arch Intern Med 2004;164:1237-41.34. Douglas RM, Hemila H, D’Souza R, Chalker EB, Treacy B. Vitamin C for preventing and treating the common cold. Cochrane Database Syst Rev2004;(4):CD000980.35. Eby GA, Davis DR, Halcomb WW. Reduction in duration of commoncolds by zinc gluconate lozenges in a double-blind study. AntimicrobAgents Chemother 1984;25:20-4.36. Marshall I. Zinc for the common cold. Cochrane Database Syst Rev1999;(2):CD001364.37. Singh M. Heated, humidified air for the common cold. Cochrane Data-base Syst Rev 2004;(2):CD001728.38. Guppy MP, Mickan SM, Del Mar CB. “Drink plenty of fluids”: a system-atic review of evidence for this recommendation in acute respiratoryinfections. BMJ 2004;328:499-500.
Last edited by Trauma1; 12-23-2008 at 05:45 PM.
Evolutionary Muse - Inspire to Evolve
09-12-2007, 11:53 PM
Zinc Gluconate Lozenges for Treating the Common Cold
A Randomized, Double-Blind, Placebo-Controlled Study
Sherif B. Mossad, MD; Michael L. Macknin, MD; Sharon V. Mendendorp, MPH; and Pamela Mason, BSN, MBA
15 July 1996 | Volume 125 Issue 2 | Pages 81-88
Background: The common cold is one of the most frequent human illnesses and is responsible for substantial morbidity and economic loss. No consistently effective therapy for the common cold has been well documented, but evidence suggests that several possible mechanisms may make zinc an effective treatment.
Objective: To test the efficacy of zinc gluconate lozenges in reducing the duration of symptoms caused by the common cold.
Design: Randomized, double-blind, placebo-controlled study.
Setting: Outpatient department of a large tertiary care center.
Patients: 100 employees of the Cleveland Clinic who developed symptoms of the common cold within 24 hours before enrollment.
Intervention: Patients in the zinc group (n = 50) received lozenges (one lozenge every 2 hours while awake) containing 13.3 mg of zinc from zinc gluconate as long as they had cold symptoms. Patients in the placebo group (n = 50) received similarly administered lozenges that contained 5% calcium lactate pentahydrate instead of zinc gluconate.
Main Outcome Measures: Subjective daily symptom scores for cough, headache, hoarseness, muscle ache, nasal drainage, nasal congestion, scratchy throat, sore throat, sneezing, and fever (assessed by oral temperature).
Results: The time to complete resolution of symptoms was significantly shorter in the zinc group than in the placebo group (median, 4.4 days compared with 7.6 days; P < 0.001). The zinc group had significantly fewer days with coughing (median, 2.0 days compared with 4.5 days; P = 0.04), headache (2.0 days and 3.0 days; P = 0.02), hoarseness (2.0 days and 3.0 days; P = 0.02), nasal congestion (4.0 days and 6.0 days; P = 0.002), nasal drainage (4.0 days and 7.0 days; P < 0.001), and sore throat (1.0 day and 3.0 days; P < 0.001). The groups did not differ significantly in the resolution of fever, muscle ache, scratchy throat, or sneezing. More patients in the zinc group than in the placebo group had side effects (90% compared with 62%; P < 0.001), nausea (20% compared with 4%; P = 0.02), and bad-taste reactions (80% compared with 30%; P < 0.001).
Conclusion: Zinc gluconate in the form and dosage studied significantly reduced the duration of symptoms of the common cold. The mechanism of action of this substance in treating the common cold remains unknown. Individual patients must decide whether the possible beneficial effects of zinc gluconate on cold symptoms outweigh the possible adverse effects.
The common cold is one of the most frequently occurring human illnesses in the world. More than 200 viruses can cause common colds in adults, including rhinoviruses (the most frequent cause), coronaviruses, adenoviruses, respiratory syncytial virus, and parainfluenza viruses. In the United States each year, adults develop an average of two to four colds and children develop an average of six to eight colds [1, 2]. The morbidity resulting from this disease and the subsequent financial loss in terms of working hours are substantial . Many previously described treatments have not provided consistent or well-documented relief of symptoms. Even a treatment that is only partially effective in relieving cold symptoms could markedly reduce physical malaise and economic losses in a large population.
The medical literature describes many possible mechanisms by which zinc may treat the common cold, and seven controlled trials have studied the use of zinc for this purpose. All seven were double-blind, placebo-controlled studies, but each used different formulations and dosages of zinc. Three of these studies showed that zinc had a beneficial effect [4-6] and four did not [7-10]. In the studies that examined virus shedding [5, 7], zinc treatment had no effect on this shedding.
We designed a study similar to that of Godfrey and colleagues  and used the symptom score developed by these researchers. We emphasized starting treatment within 24 hours after the onset of symptoms, because Godfrey and colleagues found that early treatment was most effective. We used zinc gluconate lozenges, which appeared to be well tolerated and had the best bioavailability profile in previous studies. Other studies [4-7, 9] used lozenges containing 23 mg of zinc. To improve palatability, lozenges in our study contained 13.3 mg of zinc. This provided a local concentration of zinc ions of about 4.4 mmol/L, an amount greater than that necessary to suppress rhinovirus (0.1 mmol/L) [11, 12]. The placebo lozenge contained 5% calcium lactate so that it had a medicinal taste similar to that of the zinc gluconate lozenge.
Ours was a pragmatic study designed to determine the efficacy of zinc gluconate lozenges in reducing clinical symptom scores under conditions that reflected usual medical care for the common cold [13, 14]. We did not seek to define the mechanism of any zinc effect. Although virus cultures or serologic tests might have been desirable, we decided not to do these tests because they are almost never done in the course of standard care.
Last edited by Trauma1; 10-01-2008 at 08:30 PM.
Evolutionary Muse - Inspire to Evolve
09-12-2007, 11:56 PM
Vitamin C for preventing and treating the common cold
Douglas RM, Hemilä H, Chalker E, Treacy B
Vitamin C for preventing and treating the common cold
The term 'the common cold' does not denote a precisely defined disease, yet the characteristics of this illness are familiar to most people. It is a major cause of visits to a doctor in Western countries and of absenteeism from work and school. It is usually caused by respiratory viruses for which antibiotics are useless. Other potential treatment options are of substantial public health interest.
Since vitamin C was isolated in the 1930s it has been proposed for respiratory infections, and became particularly popular in the 1970s for the common cold when (Nobel Prize winner) Linus Pauling drew conclusions from earlier placebo-controlled trials of large dose vitamin C on the incidence of colds. New trials were undertaken.
This review is restricted to placebo-controlled trials testing at least 0.2 g per day of vitamin C. Thirty trials involving 11,350 participants suggest that regular ingestion of vitamin C has no effect on common cold incidence in the ordinary population. It reduced the duration and severity of common cold symptoms slightly, although the magnitude of the effect was so small its clinical usefulness is doubtful. Nevertheless, in six trials with participants exposed to short periods of extreme physical or cold stress or both (including marathon runners and skiers) vitamin C reduced the common cold risk by half.
Trials of high doses of vitamin C administered therapeutically (starting after the onset of symptoms), showed no consistent effect on either duration or severity of symptoms. However, there were only a few therapeutic trials and their quality was variable. One large trial reported equivocal benefit from an 8 g therapeutic dose at the onset of symptoms, and two trials using five-day supplementation reported benefit. More therapeutic trials are necessary to settle the question, especially in children who have not entered these trials.
This is a Cochrane review abstract and plain language summary, prepared and maintained by The Cochrane Collaboration, currently published in The Cochrane Database of Systematic Reviews 2007 Issue 3, Copyright © 2007 The Cochrane Collaboration. Published by John Wiley and Sons, Ltd.. The full text of the review is available in The Cochrane Library (ISSN 1464-780X).
This record should be cited as: Douglas RM, Hemilä H, Chalker E, Treacy B. Vitamin C for preventing and treating the common cold. Cochrane Database of Systematic Reviews 2004, Issue 4. Art. No.: CD000980. DOI: 10.1002/14651858.CD000980.pub3
This version first published online: October 18. 2004
Date of last subtantive update: May 14. 2007
The role of vitamin C (ascorbic acid) in the prevention and treatment of the common cold has been a subject of controversy for 60 years, but is widely sold and used as both a preventive and therapeutic agent.
To discover whether oral doses of 0.2 g or more daily of vitamin C reduces the incidence, duration or severity of the common cold when used either as continuous prophylaxis or after the onset of symptoms.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 4, 2006); MEDLINE (1966 to December 2006); and EMBASE (1990 to December 2006).
Papers were excluded if a dose less than 0.2 g per day of vitamin C was used, or if there was no placebo comparison.
Data collection and analysis
Two review authors independently extracted data and assessed trial quality. 'Incidence' of colds during prophylaxis was assessed as the proportion of participants experiencing one or more colds during the study period. 'Duration' was the mean days of illness of cold episodes.
Thirty trial comparisons involving 11,350 study participants contributed to the meta-analysis on the relative risk (RR) of developing a cold whilst taking prophylactic vitamin C. The pooled RR was 0.96 (95% confidence intervals (CI) 0.92 to 1.00). A subgroup of six trials involving a total of 642 marathon runners, skiers, and soldiers on sub-arctic exercises reported a pooled RR of 0.50 (95% CI 0.38 to 0.66).
Thirty comparisons involving 9676 respiratory episodes contributed to a meta-analysis on common cold duration during prophylaxis. A consistent benefit was observed, representing a reduction in cold duration of 8% (95% CI 3% to 13%) for adults and 13.6% (95% CI 5% to 22%) for children.
Seven trial comparisons involving 3294 respiratory episodes contributed to the meta-analysis of cold duration during therapy with vitamin C initiated after the onset of symptoms. No significant differences from placebo were seen. Four trial comparisons involving 2753 respiratory episodes contributed to the meta-analysis of cold severity during therapy and no significant differences from placebo were seen.
The failure of vitamin C supplementation to reduce the incidence of colds in the normal population indicates that routine mega-dose prophylaxis is not rationally justified for community use. But evidence suggests that it could be justified in people exposed to brief periods of severe physical exercise or cold environments.
Last edited by Trauma1; 10-01-2008 at 08:31 PM.
Evolutionary Muse - Inspire to Evolve
09-13-2007, 12:00 AM
Vitamin C May Be Effective Against Common Cold Primarily in Special Populations CME/CE
News Author: Laurie Barclay, MD
CME Author: Penny Murata, MD
Release Date: July 24, 2007; Valid for credit through July 24, 2008 Credits Available
Physicians - maximum of 0.5 AMA PRA Category 1 Credit(s)™ for physicians;
Family Physicians - up to 0.5 AAFP Prescribed credit(s) for physicians;
Nurses - 0.5 nursing contact hours (0.5 contact hours are in the area of pharmacology)
July 24, 2007 — Vitamin C (ascorbic acid) may be effective against the common cold primarily in special populations, according to the results of a systematic Cochrane review published online in the July 18 issue of the Cochrane Database of Systematic Reviews. Most evidence suggests that an oral dose of 0.2 g or more of vitamin C is ineffective in treatment in the general population but may be effective in prevention, especially in special populations.
"In 'ordinary people,' vitamin C does not prevent colds," lead author Harri Hemilä, MD, PhD, an associate professor of Public Health at the University of Helsinki in Finland, told Medscape. "This is an important conclusion because lots of 'ordinary people' are taking vitamin C with the belief that vitamin C prevents colds. But there seem to be some groups of people who seem to get the benefit of vitamin C supplementation for a preventive purpose: people under heavy short-term physical stress are the most explicit group, which we identified in our Cochrane review."
Although vitamin C is widely used to prevent and treat cold symptoms, whether available evidence supports this common wisdom has been a subject of controversy.
"Despite 60 years of research in this area, there still seems to be little evidence to support the use of vitamin C in prevention or treatment of the common cold," Sherif Beniameen Mossad, MD, FACP, FIDSA, from Cleveland Clinic of Case Western Reserve University in Ohio, told Medscape. Dr. Mossad was not involved in the current Cochrane review but was asked by Medscape for independent commentary.
"However, given the significant heterogeneity of studies, and the shown benefit in certain situations, the possibility of benefit in other situations, or using different dosage or frequency should not be discarded," Dr. Mossad said. "Even if the only evidence of benefit for the individual that can be shown is what has been concluded from the current review, translating that to the benefit for the society is significant."
Using the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1966 to December 2006), and EMBASE (1990 to December 2006), the authors identified placebo-controlled trials studying the effects of 0.2 g or more per day of vitamin C for cold prevention and treatment.
Two of the authors independently extracted data from these trials and evaluated their quality. Primary outcomes were incidence of colds during prophylaxis, defined as the percentage of participants having at least 1 cold during the trial period, and duration, defined as the mean number of days of illness of cold episodes.
Meta-analysis of the relative risk (RR) of developing a cold while taking prophylactic vitamin C included data from 11,350 study participants enrolled in 30 trials. In this meta-analysis, the pooled RR was 0.96 (95% confidence intervals [CI], 0.92 - 1.00).
However, in a subgroup of 6 trials enrolling a total of 642 marathon runners (4 trials), Swiss schoolchildren in a skiing camp (1 trial), and Canadian soldiers performing subarctic exercises (1 trial), pooled RR was 0.50 (95% CI, 0.38 - 0.66), which was a highly statistically significant effect.
"The 50% average for 6 studies implies benefit for some physically stressed groups of people," Dr. Hemilä said. "Our finding of 50% suggests a clinically important benefit, but I do not believe that this figure is valid for all athletes.... The groups of people who benefit — more accurately defined, how much they benefit and how much vitamin C they should take, are questions requiring further study."
In a meta-analysis of common cold duration that included 30 comparisons involving 9676 respiratory episodes, there was a consistent benefit during prophylaxis with vitamin C, with cold duration decreased by 8% (95% CI, 3% - 13%) in adults and by 13.6% (95% CI, 5% - 22%) in children.
"These findings imply that vitamin C may prevent colds when taken prophylactically in certain situations only, and reduce the duration of colds in those who develop one while taking it prophylactically, but to a small extent; more so in children than adults," Dr. Mossad said. "It has not been shown to decrease the duration or severity of colds when taken therapeutically after the onset of illness."
Interestingly, Dr. Hemilä noted that dosages in most of the adult and child studies of prophylaxis were 1 g of vitamin C per day.
"The regular supplementation studies found strong evidence that vitamin C shortens the duration of colds that occur during supplementation," Dr. Hemilä said. "Regular [supplementation] means administering vitamin C every day over the study.... I think that the adult vs children difference in [these] studies (8% vs 13.6%) is not a real subgroup difference, but is caused by the different dose per weight."
When vitamin C was started after the onset of cold symptoms, there were no significant differences from placebo in cold duration during therapy, based on 7 trial comparisons involving 3294 respiratory episodes. Similarly, in 4 trial comparisons involving 2753 respiratory episodes, vitamin C was no different than placebo in terms of cold severity during therapy.
"There are not many therapeutic studies, with supplementation starting after the onset of symptoms, and the results are not consistent," Dr. Hemilä said. "Thus, the regular supplementation studies show that vitamin C affects the duration and severity of colds, but they do not help in evaluating its practical relevance."
One study of particular importance, according to Dr. Hemilä, was performed at the National Institutes of Health by Karlowski and colleagues and published in the March 1975 issue of Journal of the American Medical Association. In a 2 × 2 factorial design, subjects received placebo, 3 g/day of prophylactic vitamin C, 3 g/day of therapeutic vitamin C for 5 days, or 3 g/day of prophylactic vitamin C plus 3 g/day of therapeutic vitamin C.
Although the authors concluded that there were no substantial differences in the effect of regular and therapeutic supplementation on the duration of colds, Dr. Hemilä reanalyzed their data and published the findings in the October 1996 issue of the Journal of Clinical Epidemiology. The 3-g/day groups had approximately the same effect and the 6-g/day group had twice this effect (17% reduction in colds), suggesting dose dependency.
"It is noteworthy that the regular supplementation study estimates (8% and 13%) are based on studies mainly using 1 g/day," Dr. Hemilä said. "Thus, these estimates should not be used as a basis to make a decision whether vitamin C is reasonable for therapy or not. Furthermore, it is a subjective issue of values and price of treatment when a person considers whether the minimum effect should be 10% or 20% or something else."
Strengths of the current Cochrane review, according to Dr. Hemilä, are the large number of placebo-controlled studies in different countries enrolling both adults and children. The main limitation is that the therapeutic effect cannot be properly estimated from the published studies because there are few therapeutic studies and they are methodologically diverse. Another limitation is that essentially all the studies were performed in developed countries where the usual dietary intake of vitamin C is high.
Dr. Mossad added that the main strengths of this review are the "extensive personal experience and insight of the authors into this topic" and the "rigorous" methodology. The limitations result from the heterogeneity of studies included with respect to diet, living conditions, climate, dose and duration of therapy.
"There is lots of individual-level experimentation in medicine," Dr. Hemilä explained. "For example, if a antihypertensive drug does not lower blood pressure in 1 person, we try another drug; we do not say that the lack of effect in 1 person is evidence that the first drug is ineffective in general. We say that it does not work for that particular person."
"With similar kind of reasoning I think vitamin C may be tried for treating colds," Dr. Hemilä concluded. "If a person does not feel there is any benefit, he or she need not take it next time. But if vitamin C seems to be helpful, there is a subjective reason to try it again the next time."
In terms of future research, Dr. Hemilä recommended well-planned therapeutic trials of vitamin C dosages well above 1 g/day, because some studies have suggested a dose-response effect with dosages up to 6 g/day. He also recommends a study duration of longer than 5 days, because a few 3-day therapeutic trials found no benefit, and he believes that the negative findings may have been caused by the short study duration.
"More accurate characterization of the 'physical stress' group needs much more research, but I think it is less important from the public health point of view compared with the therapeutic effect mentioned above," Dr. Hemilä said. "Marathon and comparable events are rare, whereas the common cold is ubiquitous among 'ordinary' people."
Dr. Mossad also recommended prophylaxis studies in other populations or under conditions that increase the risk of having colds or of having more severe colds; treatment studies in homogenous populations using a variety of experiments using larger doses, consistent early administration, or more frequent dosing; treatment studies in children; and basic science studies to further elucidate the potential biological effect of vitamin C in preventing or treating the common cold.
"It is somewhat reassuring that serious side effects have not been encountered in any of these studies," Dr. Mossad concluded. "However, as common as the common cold is, even a rare side effect may become more apparent if consistent widespread use is implemented."
Dr. Hemilä has disclosed receiving his salary from the University of Helsinki. He holds no shares and has no other financial relationships with pharmaceutical or other companies that might have interest in vitamin C or in the common cold. He has on a few occasions lectured in meetings organized by drug companies, most recently in 2004. Dr. Mossad has disclosed no relevant financial relationships.
Cochrane Database Syst Rev. Published online July 18, 2007.
In the November 1971 issue of Proceedings of the National Academy of Sciences of the United States of America, a meta-analysis by Pauling indicated that vitamin C decreased the incidence of the common cold. Subsequent studies had variable results. Cochrane reviews on vitamin C for preventing and treating the common cold were published in 1998 and in 2004 by Douglas and colleagues (Cochrane Database of Systematic Reviews, issues 1 and 4, respectively). The 2004 review included studies from the 2004 CENTRAL database, MEDLINE from January 1966 to June 2004, EMBASE from 1990 to June, week 23, 2004, reference lists from systematic reviews, and a personal reference list from 1 reviewer. A limitation of the review was counting the placebo group multiple times in the pooled data. One additional publication, by Sasazuki and colleagues and published in the January 2006 issue of the European Journal of Clinical Nutrition, has been included in the current 2007 review, which includes search results through December 2006.
This current Cochrane review examines whether at least 0.2 g of daily prophylactic vitamin C affects the incidence, duration, or severity of the common cold and whether vitamin C treatment at the onset of the common cold affects the duration or severity of symptoms. In this review, placebo groups were counted only once in pooling data from trials with multiple treatment groups.
56 studies were found using CENTRAL (The Cochrane Library, issue 4, 2006), MEDLINE (2004 to December 2006), and EMBASE (1990 to December 2006) databases.
Criteria for inclusion were placebo-controlled trials of at least 0.2 g of vitamin C daily to prevent or treat the common cold and adequate description of methodology and data.
Studies had to include adequate information to assess study quality based on allocation concealment, blinding, randomization, attrition, and placebo distinguishability.
Subjects included children and adults of any sex or age.
3 small laboratory studies that exposed subjects to viruses after prophylactic vitamin C or placebo were not included in meta-analysis:
1 study showed decreased incidence and symptom severity score in vitamin C group.
1 study showed decreased severity, but not duration, in vitamin C group.
1 study showed no beneficial effect in vitamin C group.
42 community studies evaluated the effect of prophylactic vitamin C on naturally acquired common cold.
11 community studies evaluated the effect of treatment with vitamin C after onset of naturally acquired common cold.
Prophylactic vitamin C had no effect on common cold incidence:
Of 11,350 subjects, 6135 subjects used vitamin C for 2 weeks to 5 years.
Pooled RR for cold infection was 0.96 (95% CI, 0.92 - 1.00).
Subgroup analysis of 6 studies showed decreased cold incidence in subjects with extreme physical or cold stress or both (marathon runners, skiers, soldiers in subarctic exercise; RR, 0.50; 95% CI, 0.38 - 0.66).
Prophylactic vitamin C decreased duration of common cold:
In 7242 illness episodes in adults, pooled decrease in duration was 8.0% (95% CI, 3.0% - 13.1%).
In 2434 illness episodes in children, pooled decrease in duration was 13.6% (95% CI, 5.6% - 21.6%).
Prophylactic vitamin C slightly and inconsistently decreased severity of common cold:
Severity measured as days confined indoors or off from work or school decreased (P = .02).
Severity measured as symptom severity score did not decrease.
Pooled severity, measured as days off and symptom score, decreased (P = .004).
Treatment with vitamin C after onset of common cold did not decrease duration of symptoms in data from 3294 illness episodes:
In 1 study, illness duration of only 1 day was more common with vitamin C at 8 g/day vs 4 g/day (46% vs 39%; P = .046) and illness duration was shorter if treated with vitamin C within 24 hours of illness vs with other medications (3.6 vs 6.9 days).
Treatment with vitamin C after onset of common cold did not decrease severity of symptoms in data from 2753 illness episodes.
No serious adverse events were reported.
Adverse effects were similar for 2490 subjects receiving high-dose vitamin C (1 g/day) vs 2066 subjects receiving placebo (5.8% vs 6.0%).
Exclusion of studies with inadequate allocation concealment had no significant effect.
Pearls for Practice
The effects of oral prophylactic vitamin C on the common cold include decrease in duration, especially in children; slight decrease in severity; and no decrease in incidence, except for a subgroup of persons exposed to extreme cold or physical stress.
Vitamin C treatment of the common cold has no significant effect on duration or severity of illness.
Medscape Medical News 2007. ©2007 Medscape
Last edited by Trauma1; 10-01-2008 at 08:31 PM.
Evolutionary Muse - Inspire to Evolve
09-13-2007, 09:34 AM
09-13-2007, 09:39 AM
09-13-2007, 09:47 AM
09-13-2007, 09:52 AM
01-25-2008, 02:58 AM
I came across some good info on natural immune system enhancers/boosters ranging from dietary supplements, herbs, vitamins, and minerals. These can be used to help limit duration/severity of common cold symptoms.
Immune System Supplements
Echinacea is a plant native to the United States. The word Echinacea actually comes from a Greek word 'echinos,' which means sea urchin and refers to the plant's sea-urchin-shaped, flowering head. It was recognized over a century ago as a natural infection fighter. Echinacea is an immunostimulant in that it enhances the immune system. Evidence shows that it stimulates the body to produce more infection-fighting white blood cells, such as T-lymphocytes and killer white blood cells. It may also stimulate the release of interferons, one of the body's most potent infection-fighting weapons. Interferon kills germs and also infiltrates their genetic control center, preventing them from reproducing. Besides helping the body produce more infection- fighting cells, echinacea helps these cells to produce more germ-eating cells, called macrophages, and it helps these cells eat the germs more voraciously, a process called phagocytosis. Echinacea also prevents bacteria from secreting an enzyme called hyaluronidase, which enables them to break through protective membranes, such as the lining of the intestines and respiratory tract, and invade tissues. Echinacea also seems to search out and destroy some viruses, such as the common cold and flu viruses.
Many clinical studies demonstrate Echinacea’s efficacy as an immune system stimulant. According to the authors of a 1999 meta-analysis Echinacea is effective against respiratory infections, especially if taken as soon as the first symptoms appear.
Beta Glucan is a natural, branched polysaccharide (a molecule made up of many sugar units). It is composed of glucose molecules extracted and purified from the cell wall of common baker’s yeast. Beta Glucan enhances immunity by binding to macrophages and other phagocytic white blood cells at certain receptors and activating their anti-infection and anti-tumor activity by stimulating the production of free radicals. This stimulation signals the phagocytic immune cells to engulf and destroy foreign bodies, be they bacteria, viruses or tumor cells.
Garlic(Allium sativum) is one of the best antiviral, antibacterial, antifungal, anticancer, and cardiovascular tonics. Allicin is a sulphur compound in garlic with well-known, strong antibiotic effects.
A traditional home remedy for colds is to eat two cloves of raw garlic at the onset of symptoms. If you swallow chopped garlic but don't chew it, it’s said the garlic odour won't stay on your breath.
Probiotics: (RPN'S GUT HEALTH)
Bacteria that are friendly to the human body are necessary for proper development of the immune system, protection against disease-causing agents, and for better digestion and absorption of food and nutrients. Friendly bacteria come from two main groups, lactobacillus or bifidobacterium.
Immune System Minerals
Zinc is an essential mineral that is necessary for the functioning of over 300 different enzymes. As well as it’s involvement in carbohydrate, protein, fat and energy metabolism, it has been shown to support the immune system. -lymphocytes are white blood cells that help fight infection and depend on zinc for their development and activation. In humans, zinc deficiency can result in a decreased number of T-lymphocytes and a diminished ability to fight infection and heal wounds. Because supplemental zinc may help fight infection and heal wounds, zinc status is especially important for patients with conditions such as HIV infection.
Iron is present in every cell. It is a component of hemoglobin in red blood cells, binding the oxygen that the blood circulates throughout the body. We need iron for strength and vigor, and the element plays a key role in DNA and enzyme synthesis and other basic life processes. Numerous studies indicate that a lack of iron lowers immunity. Adequate levels help maintain cellular immunity and help to protect against some infections. Cell-mediated immune response may be impaired when iron deficiency negatively impacts the iron-requiring enzyme called ribonculeotide reductase, an enzyme that appears to be essential for the proper function of the T-lymphocyte arm of immunity. Resistance to candida, herpes simplex virus and some other pathogens appears to be reduced in those with poor iron status. On the other hand, excess iron may predispose individuals to some infections.
Magnesium is required for more than 300 enzymatic reactions in the body; that alone makes it important to the immune system. Magnesium keeps inflammatory factors in check, reducing pain and swelling of fibromyalgia and osteoarthritis.
Selenium deficiency may be the cause of cancer. It was found that women who live in areas where the soil selenium levels were poor had higher rates of cancer per capita. South western British Columbia is one of those areas. In Africa, the worst rates of HIV are in areas where soil selenium levels are very low. Selenium is needed to fight off bacteria and viruses and ensure our T-cells and NK cells work hard.
Immune System Vitamins
This vitamin enhances resistance to infection by increasing phagocytic cell migration and lymphocyte proliferation. It also enhances responsiveness to antigenic stimuli. Deficiencies have been shown to decrease lymphocyte activation, lower lysozyme and complement levels (both important chemicals of the immune system), impair secretory IgA production (especially important in the intestinal tract) and decrease T-cell dependent antibody responses.
Beta-carotene appears to selectively increase T-4 cells, reacts with free radicals and free oxygen to help prevent genetic and cell wall damage, increases tumor necrosis factor, increases activity of macrophage and natural killer (NK) cells. This changes into vitamin A as the body requires it.
Research suggests that supplementation with Vitamin A may reverse post-operative immunosuppression as well as boosting immune responses in the elderly, persons with parasitic infections and persons with high exposure to ultraviolet light.
Vitamin B2: Deficiency results in decreased ability to produce antibodies. This vitamin may be depleted by certain drugs.
Vitamin B5: Deficiency results in atrophy and loss of function of thymus gland.
Vitamin B6: Deficiency inhibits cell-mediated immune functions and antibody production, atrophy of spleen and thymus. Folic Acid: Deficiency impairs lymphocyte function and decreases antibody production.
Vitamin B12: B12 is required for proper lymphocyte function and the production of DNA and amino acids (protein).
White blood cells use Vitamin C to combat infections, and in the face of inflammation or microbial challenge, levels of Vitamin C are depleted. Animals — with the exception of guinea pigs — have the ability to manufacture extra Vitamin C in their livers to replete their stores — but humans and their distant rodent relatives lack the crucial enzyme that synthesizes C. Thus, when confronted by stress, we need additional outside sources of Vitamin C.
To determine whether vitamin C can alter the function of the immune system and provide increased protection from viral infection, Susan Ritter, MD, PhD candidate, and Gailen D. Marshall, Jr., MD, PhD, both from the University of Texas Health Science Center, studied the white blood cells of 12 patients before and after each patient took one gram of vitamin C daily for two weeks. Researchers then analyzed the immune cell types present in the blood as well as the ability of these cells to make antiviral compounds.
The number of NK cells (a cell that protects against viruses) in the peripheral blood increased after two weeks of supplementation with Vitamin C. While the number of T cells (also active in antiviral immunity) remained the same, they were more activated following vitamin C supplementation. The T cells also produced significantly more interferon-gama (an antiviral compound) and less interleukin-4 and interleukin-10 (both of which are associated with allergic disease) after two weeks of supplementation with vitamin C.
Researchers concluded that this data suggests an increase in antiviral immunity after two weeks of 1g/day vitamin C supplementation and the possible use of vitamin C to modulate the immune system in people.
This vitamin increases resistance to infection, increases antibody levels, stimulates B-lymphocytes and promotes T-4 activity and protects vitamins A, C and B-complex from destruction. It is a free radical scavenger and will protect all cell membranes and genetic material from damage from free radicals.
In a 1997 study, Meydani, et al gave healthy elderly subjects 60 mg, 200mg or 800 mg Vitamin E for 235 days in a double-blind study. While immunoglobulin levels and levels of T and B cells were unaffected, certain clinically relevant indices of cell-mediated immunity improved at the 200 mg dosage level. This suggests that the elderly may benefit from higher levels of Vitamin E than those usually recommended.
Herbs For The Immune System
Astragalus has been used by traditional Chinese practitioners as a herbal tonic for strengthening the body. Derived from the root of the perennial Astragalus membranaceus, Astragalus is native to Northern China. Huang Qi, as it is traditionally called, is believed to be a superior tonic for replenishing vital energy and strengthening the Wei Chi or 'defensive energy' of the body.
In the United States, astragalus has been the subject of much study in recent years. Studies at the University of Houston have shown that astragalus may help improve immunity function in cancer patients by increasing T-cell counts.
Research shows Astragalus root stimulates the immune system in many ways. It increases the number of stem cells in bone marrow and lymph tissue and encourages their development into active immune cells. It appears to help trigger immune ceils from a "resting" state into heightened activity. One study showed Astragalus root helps promote and maintain respiratory health. It also enhances the body's production of immunoglobulin and stimulates macrophages. Astragalus can help activate T-cells and natural killer (NK) cells.
The Andrographis genus of plants are a small, shrub-like herb which are commonly found in central Asia. Only a few of the 28 species of Andrographis have been shown to have medicinal value. The most popular of these is Andrographis paniculata (A.paniculata). This particularly bitter tasting herb is also known throughout the Asian world as ‘Bhui-nem’, because it has a similar appearance and taste to Neem (Azadirachta indica).
A.paniculata is a popular over the counter alternative treatment for the common cold. Clinical studies have confirmed that the herb can aid in terms of sleeplessness, nasal drainage and sore throat. Studies have also shown that A. paniculata enhances the body’s ability to resist infection by stimulating the production of antibodies and macrophages - large white blood cells that scavenge foreign matter. Tiredness, shivering and muscular ache have also been reduced with the use of A.panicula.
Regular consumption of ginseng has many well documented benefits, including increased energy, stress resistance and enhanced libido. It’s use an aid to recovery from illness and injury and to counter fatigue is also well established. However, to date ginseng’s beneficial effect on the immune system has not been widely studied. Yet, some evidence of it’s efficacy as an immunity booster does exist
In 1999 animal study, ginseng appeared to stimulate the function of certain immune cells to help clear bacterial infection. In another human study, those receiving daily ginseng supplements prior to flu vaccination were less likely to contract the flu than those in the control group, who were administered
Siberian ginseng may help the body deal with physically and mentally stressful exposures such as viruses that cause the flu. By strengthening your system, it may, in theory, also help prevent viral illnesses. In fact, a 4-week study of healthy people found that those who received Siberian ginseng extract had improvements in a number of measures that reflect the functioning of the immune system. Also, in laboratory studies, an extract of Siberian ginseng slowed the replication of certain viruses, including influenza A (which causes the flu) as well as human rhinovirus and respiratory syncytial virus (both of which cause symptoms of the common cold). These findings don't guarantee that you will be less likely to develop colds and flus if you take Siberian ginseng, but they do suggest that that is possible. More research to test this idea would be interesting.
Eucalyptus is commonly used in remedies to treat the symptoms of cold or flu, particularly cough. It can be found in many lozenges, cough syrups, and vapor baths throughout the United States and Europe. Herbalists recommend the use of fresh leaves in teas and gargles to soothe sore throats. Ointments containing eucalyptus leaves are also applied to the nose and chest to relieve congestion. Eucalyptus oil helps loosen phlegm, so many herbal practitioners recommend inhaling eucalyptus vapors to help treat coughs and the flu. Teas containing eucalyptus leaves have also been used traditionally to reduce fevers
Immune Boosting Antioxidants
Alpha Lipoic Acid:
A potent antioxidant that is a more effective detoxifier than even vitamin C and vitamin E. It is well researched for the treatment of diabetes as it improves insulin sensitivity and controls diabetic neuropathies. Studies have shown that lipoic acid is an important vitamin-like nutrient that inhibits the ability of viruses to replicate.
No other antioxidant is as important to overall health as glutathione. It is the regenerator of immune cells and the most valuable detoxifying agent. Low levels are associated with early death and viral infections. Optimal levels control insulin, halt inflammatory processes, detoxify alcohol, eliminate carcinogens and keep cholesterol from oxidizing.
Coenzyme Q10 has been found to halt tumors and have antibacterial and antiviral properties. By the time we are 50 our coenzyme Q10 levels are half the levels of our 20s. Thirty mg per day is a maintenance dose, but over 320 mg has been used in research to treat breast cancer with excellent tumor-inhibiting action.
The black elderberry (Sambucas nigra) is well established for its antioxidant and healing properties. In recent years it has also been found to significantly assist sufferers of flu and cold symptoms to get better. Researchers believe that the black elderberry enhances the immune system by stimulating cytokine production. These unique proteins act as messengers in the immune system to help regulate immune response, thus helping to defend the body against disease.
Evolutionary Muse - Inspire to Evolve
01-25-2008, 01:04 PM
Here's a study that demonstrated probiotics ability to shorten the duration of the common cold(rhinovirus.)
Vaccine. 2006 Nov 10;24 (44-46):6670-4 16844267
Probiotic bacteria reduced duration and severity but not the incidence of common cold episodes in a double blind, randomized, controlled trial. [My paper] Michael de Vrese , Petra Winkler , Peter Rautenberg , Timm Harder , Christian Noah , Christiane Laue , Stephan Ott , Jochen Hampe , Stefan Schreiber , Knut Heller , Jürgen Schrezenmeir
To investigate the effect of long-term consumption of probiotic bacteria on viral respiratory tract infections (common cold, influenza), a randomized, double blind, controlled intervention study was performed during two winter/spring periods (3 and 5 month). Four hundred and seventy-nine healthy adults were supplemented daily with vitamins plus minerals with or without probiotic lactobacilli and bifidobacteria. The intake of the probiotic had no effect on the incidence of common cold infections (verum=158, control=153 episodes, influenza was not observed), but significantly shortened duration of episodes by almost 2 days (7.0+/-0.5 versus 8.9+/-1.0 days, p=0.045), reduced the severity of symptoms and led to larger increases in cytotoxic T plus T suppressor cell counts and in T helper cell counts.
Evolutionary Muse - Inspire to Evolve
01-25-2008, 08:23 PM
01-25-2008, 10:10 PM
I swear by the zinc.
I got hooked on the zinc lozenges back when they didn't have any technology to mask the godawful taste of Zinc Glycine Gluconate. If you could handle sucking on one of those for a half hour, you should at least get over your cold (and perhaps get paid $20).
Athletic Xtreme Rep
Ask me about the Athletic Xtreme Product Line
01-25-2008, 10:55 PM
01-25-2008, 10:56 PM
01-27-2008, 12:29 PM
Anybody else read up on the problems with Zycam for treating onset of colds (reducing time)? There is a website based on this...People losing their sense of smell/taste because of it and suing...though Zycam still being sold so I'm not sure...
01-27-2008, 12:35 PM
Is their any chance of RPN coming out with an Immunity based supplement. I would like to see one of the sponsers on this board come out with an all in one product to prevent colds or Immunity Stack type product. Not just one ingredient type product, but a synergistic blend. I'm sure everyone would be interested because you can't train when your sick and that really pisses some people off!. Who is up to the challenge?
01-27-2008, 12:50 PM
Evolutionary Muse - Inspire to Evolve
03-08-2008, 11:08 AM
Bumping this because I'm miserable. It would seem I have the flu: Fever, painful joints and skin, cough, lung pain.
I'll see what we have here thats on your list and take it all... I doubt I'll be able to get out of the driveway to make it to a store.
03-08-2008, 11:17 AM
Evolutionary Muse - Inspire to Evolve
03-08-2008, 11:18 AM
03-08-2008, 11:27 AM
03-08-2008, 11:58 AM
This is definately a great thread thats very imformative T1! Good thread as always! I have been lucky so far as far as sickness goes. Get better C and kick that flus ass!
E-Pharm Rep... PM me with any questions or concerns
03-08-2008, 12:03 PM
03-08-2008, 12:13 PM
03-08-2008, 12:41 PM
Excellent thread, T1!
Product Educator | USPowders
Statements made by this online persona are the sole property of the owner, and do not necessarily reflect USPowders’ opinion as a whole.
03-09-2008, 11:10 AM
Still wondering about an All-In-One Immunity based supplement. This would be a product you could take year round with Seasonal versions, such as "Spring- Immunity Boost". You would have make it unique to the seasonal allergies and infections typically caught during those certain times of the year. Once again, I am sure this would be a big hit. How many times have you seen those threads like "Feel like crap", or, "I'm sick, is it ok to work out"....Help is definitley needed in this area. It is just up to a supplement company to step up and do the job.
03-09-2008, 11:32 AM
09-04-2008, 10:21 PM
Omg, I've been suffering from the worst cold the last few days and I just now saw this! Damn!
Is more then one cap of Gut Health needed once you do have a cold? I've been taking at least one cap now for a couple weeks or more.
U da man Trauma!
09-04-2008, 10:42 PM
Evolutionary Muse - Inspire to Evolve
09-04-2008, 10:49 PM
I dose 2 caps a day as it is. And at 12.50/bottle, no reason not to
"I am legally blind and if I can Squat,deadlift and over all get myself to the gym then anyone can get their a$$ in gear and get strong!!" - malleus25
09-04-2008, 10:53 PM
Evolutionary Muse - Inspire to Evolve
09-04-2008, 10:55 PM
I came home to 6 new bottles
Christmas come early.
"I am legally blind and if I can Squat,deadlift and over all get myself to the gym then anyone can get their a$$ in gear and get strong!!" - malleus25
09-04-2008, 11:02 PM
09-04-2008, 11:40 PM
09-04-2008, 11:49 PM
09-04-2008, 11:52 PM
I'll be adding in a whole section looking at the pathophysiology and treatment methods utilized in modern medicine for Flu-Like illness.
The Flu season is just around the corner at this point, so get ready everyone. It's been predicted to be a bad flu season this year.
Evolutionary Muse - Inspire to Evolve
09-05-2008, 12:42 AM
superb info T1!. i bookmarked it for when i get my next cold....which i'm not planning on getting for a few years.
getting sick really set your training back.
09-05-2008, 04:55 PM
Similar Forum Threads
- By mrowe8 in forum AnabolicsReplies: 4Last Post: 12-17-2009, 05:00 AM
- By David Dunn in forum SupplementsReplies: 0Last Post: 08-19-2009, 01:15 PM
- By Delta Force in forum General ChatReplies: 35Last Post: 11-19-2008, 11:01 AM
- By avenue Red in forum Nutrition / HealthReplies: 5Last Post: 11-14-2007, 01:28 PM
- By LakeMountD in forum News and ArticlesReplies: 8Last Post: 08-03-2005, 05:08 PM