The Annual Question: What about the flu vaccine?

Jacob Schor ND, FABNO

November 21, 2011

 

 

Every fall, patients start asking us whether they ‘need’ to get a flu shot.  This is never an easy question as the term ‘need’ is so open ended. Starting in 2010, the US government started recommending  “annual influenza vaccination for all persons aged ≥6 months in the United States.”

 

In past years we have sent out newsletters describing various ‘natural options’ that are suggested to both prevent and treat colds and flu.  This year a correspondent forwarded me a variation on this question that is as much ethical as medical in nature.  Let me see if I can paraphrase the situation.

 

The writer is a nurse working at a local hospital.  She does not want to get the influenza vaccination, which the hospital wants her to, preferring to take care of herself and prevent flu naturally.

 

Her question has prompted me to make my annual review of flu treatments from a slightly different perspective and question whether the various natural interventions reduce the chance of infection or reduce the symptoms of the infection.  This is particularly relevant in her situation.  When employed caring for people who are already ill, one has a stronger moral obligation to not spread illness to those under one’s care.  There are two reasons why I say this.  First, the people a nurse cares for in a hospital are there usually because they are sick.  These people are at greater risk for serious morbidity and even mortality from a flu infection than the general population.  Influenza vaccinations are very effective at lowering risk of getting the flu, they “… prevent[s] influenza illness among approximately 70%--90% of healthy adults aged <65 years.”    Vaccines may be less effective in “… institutionalized elderly patients. According to the Centers for Disease Control (CDC), even when the match between the vaccine and the circulating virus is close, the efficacy rate of the flu vaccination drops to 30-40 % for institutionalized individuals over age 65.”

 

 

One cannot depend on vaccines to reliably protect older hospitalized patients and it becomes more important to prevent spread of infections from those who act as caretakers.

 

It is with these thoughts in mind that I approach this year’s review.

 

 

N-acetyl-cysteine (NAC) has been recommended as being protective against the flu for more than a decade.  In 1997 a human randomized control trial was published suggesting it was protective. De Flora et al from the University of Genoa, Italy reported that they had recruited 263 older subjects, more than half suffering from non-respiratory chronic degenerative diseases and enrolled them in a randomized, double-blind trial, taking either placebo or NAC tablets (600 mg) twice daily for 6 months.  Those taking NAC had a significant decrease in the frequency and intensity of influenza-like symptoms.  Yet both the NAC group and the placebo group had the same frequency of sero-conversion, that is getting infected.  Of those taking NAC, who had been virus infected, only 25% experienced symptoms.  In those taking placebo, 79% had flu-like symptoms. NAC did not prevent infection but it did significantly reduce “incidence  of clinically apparent disease.”

 

While these results are great for keeping someone feeling well, they are a concern if the person is caring for other people.  That’s because they may be unaware that they are infected and continue working and spread the disease to those unable to resist.

 

In the case of NAC the situation isn’t quite this straightforward.  It appears that NAC’s action is two-fold.  It both inhibits the production of inflammatory chemicals that trigger the symptoms of illness and also targets the virus directly, inhibiting it’s ability to reproduce.  A 2010 paper tells us that, “NAC inhibits H5N1 replication and [also] H5N1-induced production of pro-inflammatory molecules. Therefore, antioxidants like NAC represent a potential additional treatment option that could be considered in the case of an influenza A virus pandemic.”    A paper published in May 2011 adds to this information telling us that NAC will inhibit replication of some virus strains but not all of them.  Sometimes it may be helpful fighting influenza but it’s not a universal treatment for flu infections.

 

An even newer paper on the subject, from September 2011, further details how NAC blocks the symptoms of flu.  Having fewer flu symptoms is desirable for most of us, but a concern in a hospital worker who may unknowingly pass the infection to others.   It could possibly be that NAC, because it slows viral replication, will decrease the virus’ ability to infect other people but we have yet to see published evidence supporting this idea.

 

Other natural interventions may reduce flu symptoms but may not prevent infection.  It’s difficult to tell.

 

Elderberry extracts have long been popular for treating the flu.  Promoters of elderberry, cite two clinical trials in which elderberry decreased symptom intensity and duration of influenza.

 

The first study was published in the winter of 1995. In those given an elderberry extract, “… significant improvement of the symptoms, including fever, was seen in 93.3% of the cases …. within 2 days…” Those patients who received placebo instead of the elderberry took 6 days to feel better.  

 

In a second clinical trial, published in 2004, those who took the elderberry extract reported symptom relief 4 days earlier than those who took placebo.  

 

The anthocyanins in elderberry may have anti-inflammatory action in the same way that NAC does, but elderberry also acts directly against the virus infection.  According to a 2009 publication, elderberry flavonids bind to and prevent infection from H1Na infections, at least in test tube experiments.   Earlier this year another paper told us that elderberry directly inhibits both bacteria and viruses that infect the human respiratory tract.

 

These last two studies were in vitro.  Whether elderberry will do the same in people is still unclear.  Clinically our experience is that elderberry does reduce incidence of infection and duration and intensity of illness.

 

A 2007 comprehensive article in Alternative Medicine Review provides a list of other supplements that might be useful in treating or preventing influenza.  Several of these are of interest as they have been the subject of clinical trials.

 

 

The second clinical study on ginseng was published in 2004 and reported the results of two different randomized control trials over two winter seasons. Both studies were conducted in nursing homes with older participants, average age was 81 for the fist study (conducted in 2000) and 83.5 years old for the second study (2001).  Most (90%) of the participants had been vaccinated against influenza. Those participants who received placebo were nearly 8 times as likely to come down with flu than those participants taking the ginseng extract. (odds ratio (OR)=7.73, P=.033). Those taking ginseng had an almost 90% reduction in risk of respiratory infection (OR=10.50, P=.009). 

 

A 2005 trial randomly split 325 people of mixed ages and tracked how many days they were sick with colds during a long Canadian winter in Edmonton.  Those who took the placebo were sick about 50% more of the time than those who took ginseng.

 

The most recent clinical trial on ginseng used Cold Fx and was published in 2006.  Again a randomized placebo controlled trial, this time 43 seniors living in a care-facility.  Taking the ginseng “… during an early "cold and flu" season reduced the relative risk and duration of respiratory symptoms by 48% and 55%...”

 

An October 2011 report tells us that ginseng’s action may simply be inflammatory suppression, that is it prevents the expression of the symptoms of illness.   If that is the case, it may leave us in a similar quandary as the NAC.  It may keep sick people from knowing they are sick and allow them to go to work and continue spreading infection.   So while these ginseng extracts sound useful to take yourself, I’m not sure I want to be around someone taking them.  They won’t know when they are sick.

 

 

 

Vitamin D:  Starting with Hope-Simpson’s book published decades ago, there has been recognition that there is a seasonal fluctuation in influenza incidence.  Hope-Simpson predicted that ultraviolet light somehow hindered viral transmission.  It wasn’t until John Cannell’s  2008 publication that this protective effect was linked to vitamin D levels.  [free text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2279112/?tool=pubmed ]

 

Cannell’s  theory that vitamin D influences influenza has gained wide acceptance, at least in alternative medicine circles.

 

“In temperate latitudes even pandemic influenzas often show a clear seasonality. The data support the hypothesis that high fluences of UVB radiation (vitamin D level), as occur in the summer, act in a protective manner with respect to influenza.”

 

 

There is no reason to think that vitamin D only suppresses symptoms of infection, rather the assumption is that it decreases viral transmission by increasing immune resistance.   Vitamin D plays a “… critical role ….. improving barrier function, production of antimicrobial peptides including cathelicidin and some defensins, and immune modulation…”  

 

A 2011 paper tells us that, “Epidemiological studies do suggest that vitamin D deficiency predisposes to viral respiratory tract infections and mycobacterial infections and that vitamin D may play a role in the development and treatment of asthma. Randomized, placebo-controlled trials are lacking but ongoing.”  

 

While the arguments in favor of vitamin D providing protection against influenza infection are elegant the clinical trials are still limited. 

 

At this point though there is only one randomized controlled study on vitamin D and influenza. “This study suggests that vitamin D(3) supplementation during the winter may reduce the incidence of influenza A, especially in specific subgroups of schoolchildren.” Published in May 2010 this Japanese study followed 167 children taking vitamin D and an equal number taking placebo during a winter flu season. Only 10.8% of the children taking vitamin D compared to 18.6% of the kids in the placebo group got influenza [relative risk (RR), 0.58; 95% CI: 0.34, 0.99; P = 0.04]. The effect was more striking in children who had asthma.   Taking vitamin D lowered their risk of an asthma attack by 83% (RR: 0.17; 95% CI: 0.04, 0.73; P = 0.006).

 

 

It should be mentioned that a recent study, October 2011, on vitamin D did not find a protective effect.  This was not a clinical trial.  Rather participants in other trials were sent questionnaires asking about their frequency of illness. Participants from 10 different clinical trials took part, 569 in total of whom 289 had taken vitamin D and 280 had taken placebo. 38 subjects who had taken vitamin D reported influenza like disease the prior winter while 42 in the placebo group reported illness.  This was not a statistically significant difference.  There are obvious problems with this study besides the trying to recall whether one got sick a year ago.  The most obvious problem is that many participants took low doses of vitamin D, which may have been inadequate to have protective effect.

 

 

 

Umcka (Pelargonium sidoides) is a geranium plant native to South Africa. Long used in traditional African medicine, umcka (short for "umckaloabo") has recently become popular in other parts of the world, particularly in treatment of respiratory problems.  There are a dozen or so clinical trials using umcka to treat acute bronchitis with good effect.    

 

Most these papers are about bacterial bronchitis and sinusitis.  There is only one study on influenza and this was not a clinical trial.  This in vitro study published in March 2011,  tells us that umcka “interfered with replication of seasonal influenza A virus strains (H1N1, H3N2), respiratory syncytial virus, human coronavirus, parainfluenza virus, and coxsackie virus. ”

 

This is encouraging but it appears that at least some of umcka’s benefit is because it inhibits inflammatory cytokines and limit ‘sickness behavior’ but not necessarily infection.    Thus once again we may create an infectious carrier, someone who feels well but spreads illness.

 

 

Acidophilus: One randomized controlled trial published in 2009 tells us that one specific form of acidophilus, Bifidobacterium animalis subsp lactis Bi-07, decreased cold and flu-like symptoms in children. 

 

Micronutrients:

It was thought that micronutrient supplements might increase response to vaccine but a 2004 study found no difference. “A micronutrient supplement providing the reference nutrient intake administered over 8 weeks had no beneficial effect on antibody response to influenza vaccine in older people living in long-term care.” 

 

 

 

Summary:

The following supplements may mask symptoms of disease and leave someone infectious while feeling ‘well’ and should be a cause of concern in health caregivers:

 

 

 

The following natural interventions may decrease flu infection incidence by increasing immune protection or having a direct viral inhibitory effect:

 

 

 

MMWR Morb Mortal Wkly Rep. 2011 Aug 26;60(33):1128-32.

Prevention and control of influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2011.

Centers for Disease Control and Prevention (CDC).

Abstract

 

This document provides updated guidance for the use of influenza vaccines in the United States for the 2011-12 influenza season. In 2010, the Advisory Committee on Immunization Practices (ACIP) first recommended annual influenza vaccination for all persons aged ≥6 months in the United States. Vaccination of all persons aged ≥6 months continues to be recommended. Information is presented in this report regarding vaccine strains for the 2011-12 influenza season, the vaccination schedule for children aged 6 months through 8 years, and considerations regarding vaccination of persons with egg allergy. Availability of a new Food and Drug Administration (FDA)-approved intradermally administered influenza vaccine formulation for adults aged 18 through 64 years is reported. For issues related to influenza vaccination that are not addressed in this update, refer to the 2010 ACIP statement on prevention and control of influenza with vaccines and associated updates.

 

PMID:

    21866086

    [PubMed - indexed for MEDLINE]

 

 

MMWR Recomm Rep. 2006 Jul 28;55(RR-10):1-42.

Prevention and Control of Influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP).

Advisory Committee on Immunization Practices, Smith NM, Bresee JS, Shay DK, Uyeki TM, Cox NJ, Strikas RA.

Source

 

Influenza Division, National Center for Immunization and Respiratory Diseases, Atlanta, GA 30333, USA.

Altern Med Rev. 2007 Mar;12(1):25-48.

Colds and influenza: a review of diagnosis and conventional, botanical, and nutritional considerations.

Roxas M, Jurenka J.

Source

Thorne Research, PO Box 25, Dover, ID 83825, USA. m.roxas@comcast.net

Abstract

The common cold is the leading cause of doctor visits in the United States and annually results in 189 million lost school days. In the course of one year the U.S. population contracts approximately 1 billion colds. Influenza infection is still a leading cause of morbidity and mortality, accounting for 20-25 million doctor visits and 36,000 deaths per year in the United States. Conventional therapies for colds and flu focus primarily on temporary symptom relief and include over-the-counter antipyretics, anti-inflammatories, and decongestants. Treatment for influenza also includes prescription antiviral agents and vaccines for prevention. This article reviews the common cold and influenza viruses, presents the conventional treatment options, and highlights select botanicals (Echinacea spp., Sambucus nigra, larch arabinogalactan, Astragalus membranaceous, Baptisia tinctoria, Allium sativa, Panax quinquefolium, Eleutherococcus senticosus, Andrographis paniculata, olive leaf extract, and Isatis tinctoria) and nutritional considerations (vitamins A and C, zinc, high lactoferrin whey protein, N-acetylcysteine, and DHEA) that may help in the prevention and treatment of these conditions.

 

Eur Respir J. 1997 Jul;10(7):1535-41.

Attenuation of influenza-like symptomatology and improvement of cell-mediated immunity with long-term N-acetylcysteine treatment.

De Flora S, Grassi C, Carati L.

Source

Institute of Hygiene and Preventive Medicine, University of Genoa, Italy.

Abstract

N-acetylcysteine (NAC), an analogue and precursor of reduced glutathione, has been in clinical use for more than 30 yrs as a mucolytic drug. It has also been proposed for and/or used in the therapy and/or prevention of several respiratory diseases and of diseases involving an oxidative stress, in general. The objective of the present study was to evaluate the effect of long-term treatment with NAC on influenza and influenza-like episodes. A total of 262 subjects of both sexes (78% > or = 65 yrs, and 62% suffering from nonrespiratory chronic degenerative diseases) were enrolled in a randomized, double-blind trial involving 20 Italian Centres. They were randomized to receive either placebo or NAC tablets (600 mg) twice daily for 6 months. Patients suffering from chronic respiratory diseases were not eligible, to avoid possible confounding by an effect of NAC on respiratory symptoms. NAC treatment was well tolerated and resulted in a significant decrease in the frequency of influenza-like episodes, severity, and length of time confined to bed. Both local and systemic symptoms were sharply and significantly reduced in the NAC group. Frequency of seroconversion towards A/H1N1 Singapore 6/86 influenza virus was similar in the two groups, but only 25% of virus-infected subjects under NAC treatment developed a symptomatic form, versus 79% in the placebo group. Evaluation of cell-mediated immunity showed a progressive, significant shift from anergy to normoergy following NAC treatment. Administration of N-acetylcysteine during the winter, thus, appears to provide a significant attenuation of influenza and influenza-like episodes, especially in elderly high-risk individuals. N-acetylcysteine did not prevent A/H1N1 virus influenza infection but significantly reduced the incidence of clinically apparent disease.

PMID:

9230243

[PubMed - indexed for MEDLINE]

Free full tex

 

Biochem Pharmacol. 2010 Feb 1;79(3):413-20. Epub 2009 Sep 2.

N-acetyl-L-cysteine (NAC) inhibits virus replication and expression of pro-inflammatory molecules in A549 cells infected with highly pathogenic H5N1 influenza A virus.

Geiler J, Michaelis M, Naczk P, Leutz A, Langer K, Doerr HW, Cinatl J Jr.

Source

Institute of Medical Virology, Johann Wolfgang Goethe-University Frankfurt, Paul-Ehrlich-Strasse 40, 60596 Frankfurt am Main, Germany.

Abstract

The antioxidant N-acetyl-L-cysteine (NAC) had been shown to inhibit replication of seasonal human influenza A viruses. Here, the effects of NAC on virus replication, virus-induced pro-inflammatory responses and virus-induced apoptosis were investigated in H5N1-infected lung epithelial (A549) cells. NAC at concentrations ranging from 5 to 15 mM reduced H5N1-induced cytopathogenic effects (CPEs), virus-induced apoptosis and infectious viral yields 24 h post-infection. NAC also decreased the production of pro-inflammatory molecules (CXCL8, CXCL10, CCL5 and interleukin-6 (IL-6)) in H5N1-infected A549 cells and reduced monocyte migration towards supernatants of H5N1-infected A549 cells. The antiviral and anti-inflammatory mechanisms of NAC included inhibition of activation of oxidant sensitive pathways including transcription factor NF-kappaB and mitogen activated protein kinase p38. Pharmacological inhibitors of NF-kappaB (BAY 11-7085) or p38 (SB203580) exerted similar effects like those determined for NAC in H5N1-infected cells. The combination of BAY 11-7085 and SB203580 resulted in increased inhibitory effects on virus replication and production of pro-inflammatory molecules relative to either single treatment. NAC inhibits H5N1 replication and H5N1-induced production of pro-inflammatory molecules. Therefore, antioxidants like NAC represent a potential additional treatment option that could be considered in the case of an influenza A virus pandemic.

PMID:

19732754

 

J Negat Results Biomed. 2011 May 9;10:5.

N-acetylcysteine lacks universal inhibitory activity against influenza A viruses.

Garigliany MM, Desmecht DJ.

Source

Department of Pathology, Faculty of Veterinary Medicine, University of Liège, Belgium. mmgarigliany@ulg.ac.be

Abstract

N-acetylcysteine (NAC) has been recently proposed as an adjuvant therapeutic drug for influenza pneumonia in humans. This proposal is based on its ability to restrict influenza virus replication in vitro and to attenuate the severity of the disease in mouse models. Although available studies were made with different viruses (human and avian), published information related to the anti-influenza spectrum of NAC is scarce. In this study, we show that NAC is unable to alter the course of a fatal influenza pneumonia caused by inoculation of a murinized swine H1N1 influenza virus. NAC was indeed able to inhibit the swine virus in vitro but far less than reported for other strains. Therefore, susceptibility of influenza viruses to NAC appears to be strain-dependent, suggesting that it cannot be considered as a universal treatment for influenza pneumonia.

PMID:

21554703

[PubMed - indexed for MEDLINE]

PMCID: PMC3104374

Free PMC Article

 

Biochem Pharmacol. 2011 Sep 1;82(5):548-55. Epub 2011 May 25.

N-acetyl-L-cysteine (NAC) inhibit mucin synthesis and pro-inflammatory mediators in alveolar type II epithelial cells infected with influenza virus A and B and with respiratory syncytial virus (RSV).

Mata M, Morcillo E, Gimeno C, Cortijo J.

Source

Research Foundation of the University General Hospital of Valencia, Avenida Tres Cruces no. 2, Valencia, Spain. mata_manroi@gva.es

Abstract

64% of chronic obstructive pulmonary disease (COPD) exacerbations are caused by respiratory infections including influenza (strains A and B) and respiratory syncytial virus (RSV). They affect the airway epithelium increasing inflammatory and apoptosis events through mechanisms involving ROS generation, and induce the release of mucins from epithelial cells that are involved in the deterioration of the patient's health during the course of the disease. The antioxidant NAC has proved useful in the management of COPD reducing symptoms, exacerbations and accelerated lung function decline. It has been shown to inhibit influenza virus replication and to diminish the release of inflammatory and apoptotic mediators during virus infection. The main objective of this study is to analyze the effects of NAC in modulating MUC5AC over-expression and release in an in vitro infection model of alveolar type II A549 cells infected with influenza (strains A and B) and RSV. We have also analyzed virus replication and different pro-inflammatory responses. Our results indicate a significant induction of MUC5AC, IL8, IL6 and TNF-alpha that is strongly inhibited by NAC at the expression and at the release level. It also decreased the intracellular H(2)O(2) concentration and restored the intracellular total thiol contents. Mechanisms of NAC included inhibition of NF-κB translocation to the cellular nucleus and phosphorylation of MAPK p38. NAC also inhibited replication of the three viruses under study. This work supports the use of antioxidants in order to ameliorate the inflammatory effects of different viral infections during COPD exacerbations.

Copyright © 2011 Elsevier Inc. All rights reserved.

PMID:

21635874

 

J Altern Complement Med. 1995 Winter;1(4):361-9.

Inhibition of several strains of influenza virus in vitro and reduction of symptoms by an elderberry extract (Sambucus nigra L.) during an outbreak of influenza B Panama.

Zakay-Rones Z, Varsano N, Zlotnik M, Manor O, Regev L, Schlesinger M, Mumcuoglu M.

Source

Department of Virology, Hebrew University-Hadassah Medical School, Jerusalem, Israel.

Abstract

A standardized elderberry extract, Sambucol (SAM), reduced hemagglutination and inhibited replication of human influenza viruses type A/Shangdong 9/93 (H3N2), A/Beijing 32/92 (H3N2), A/Texas 36/91 (H1N1), A/Singapore 6/86 (H1N1), type B/Panama 45/90, B/Yamagata 16/88, B/Ann Arbor 1/86, and of animal strains from Northern European swine and turkeys, A/Sw/Ger 2/81, A/Tur/Ger 3/91, and A/Sw/Ger 8533/91 in Madin-Darby canine kidney cells. A placebo-controlled, double blind study was carried out on a group of individuals living in an agricultural community (kibbutz) during an outbreak of influenza B/Panama in 1993. Fever, feeling of improvement, and complete cure were recorded during 6 days. Sera obtained in the acute and convalescent phases were tested for the presence of antibodies to influenza A, B, respiratory syncytial, and adenoviruses. Convalescent phase serologies showed higher mean and mean geometric hemagglutination inhibition (HI) titers to influenza B in the group treated with SAM than in the control group. A significant improvement of the symptoms, including fever, was seen in 93.3% of the cases in the SAM-treated group within 2 days, whereas in the control group 91.7% of the patients showed an improvement within 6 days (p < 0.001). A complete cure was achieved within 2 to 3 days in nearly 90% of the SAM-treated group and within at least 6 days in the placebo group (p < 0.001). No satisfactory medication to cure influenza type A and B is available. Considering the efficacy of the extract in vitro on all strains of influenza virus tested, the clinical results, its low cost, and absence of side-effects, this preparation could offer a possibility for safe treatment for influenza A and B.

PMID:

9395631

 

 

J Int Med Res. 2004 Mar-Apr;32(2):132-40.

Randomized study of the efficacy and safety of oral elderberry extract in the treatment of influenza A and B virus infections.

Zakay-Rones Z, Thom E, Wollan T, Wadstein J.

Source

Department of Virology, Hebrew University-Hadassah Medical School, Jerusalem, Israel.

Abstract

Elderberry has been used in folk medicine for centuries to treat influenza, colds and sinusitis, and has been reported to have antiviral activity against influenza and herpes simplex. We investigated the efficacy and safety of oral elderberry syrup for treating influenza A and B infections. Sixty patients (aged 18-54 years) suffering from influenza-like symptoms for 48 h or less were enrolled in this randomized, double-blind, placebo-controlled study during the influenza season of 1999-2000 in Norway. Patients received 15 ml of elderberry or placebo syrup four times a day for 5 days, and recorded their symptoms using a visual analogue scale. Symptoms were relieved on average 4 days earlier and use of rescue medication was significantly less in those receiving elderberry extract compared with placebo. Elderberry extract seems to offer an efficient, safe and cost-effective treatment for influenza. These findings need to be confirmed in a larger study.

PMID:

15080016

 

Phytochemistry. 2009 Jul;70(10):1255-61. Epub 2009 Aug 12.

Elderberry flavonoids bind to and prevent H1N1 infection in vitro.

Roschek B Jr, Fink RC, McMichael MD, Li D, Alberte RS.

Source

HerbalScience Group LLC, 1004 Collier Center Way, Suite 200, Naples, FL 34110, USA.

Abstract

A ionization technique in mass spectrometry called Direct Analysis in Real Time Mass Spectrometry (DART TOF-MS) coupled with a Direct Binding Assay was used to identify and characterize anti-viral components of an elderberry fruit (Sambucus nigra L.) extract without either derivatization or separation by standard chromatographic techniques. The elderberry extract inhibited Human Influenza A (H1N1) infection in vitro with an IC(50) value of 252+/-34 microg/mL. The Direct Binding Assay established that flavonoids from the elderberry extract bind to H1N1 virions and, when bound, block the ability of the viruses to infect host cells. Two compounds were identified, 5,7,3',4'-tetra-O-methylquercetin (1) and 5,7-dihydroxy-4-oxo-2-(3,4,5-trihydroxyphenyl)chroman-3-yl-3,4,5-trihydroxycyclohexanecarboxylate (2), as H1N1-bound chemical species. Compound 1 and dihydromyricetin (3), the corresponding 3-hydroxyflavonone of 2, were synthesized and shown to inhibit H1N1 infection in vitro by binding to H1N1 virions, blocking host cell entry and/or recognition. Compound 1 gave an IC(50) of 0.13 microg/mL (0.36 microM) for H1N1 infection inhibition, while dihydromyricetin (3) achieved an IC(50) of 2.8 microg/mL (8.7 microM). The H1N1 inhibition activities of the elderberry flavonoids compare favorably to the known anti-influenza activities of Oseltamivir (Tamiflu; 0.32 microM) and Amantadine (27 microM).

PMID:

19682714

 

 

BMC Complement Altern Med. 2011 Feb 25;11:16.

Inhibitory activity of a standardized elderberry liquid extract against clinically-relevant human respiratory bacterial pathogens and influenza A and B viruses.

Krawitz C, Mraheil MA, Stein M, Imirzalioglu C, Domann E, Pleschka S, Hain T.

Source

Institute for Medical Microbiology, Justus-Liebig-University, Frankfurter Strasse 107, 35392 Giessen, Germany.

Abstract

BACKGROUND:

Black elderberries (Sambucus nigra L.) are well known as supportive agents against common cold and influenza. It is further known that bacterial super-infection during an influenza virus (IV) infection can lead to severe pneumonia. We have analyzed a standardized elderberry extract (Rubini, BerryPharma AG) for its antimicrobial and antiviral activity using the microtitre broth micro-dilution assay against three Gram-positive bacteria and one Gram-negative bacteria responsible for infections of the upper respiratory tract, as well as cell culture experiments for two different strains of influenza virus.

METHODS:

The antimicrobial activity of the elderberry extract was determined by bacterial growth experiments in liquid cultures using the extract at concentrations of 5%, 10%, 15% and 20%. The inhibitory effects were determined by plating the bacteria on agar plates. In addition, the inhibitory potential of the extract on the propagation of human pathogenic H5N1-type influenza A virus isolated from a patient and an influenza B virus strain was investigated using MTT and focus assays.

RESULTS:

For the first time, it was shown that a standardized elderberry liquid extract possesses antimicrobial activity against both Gram-positive bacteria of Streptococcus pyogenes and group C and G Streptococci, and the Gram-negative bacterium Branhamella catarrhalis in liquid cultures. The liquid extract also displays an inhibitory effect on the propagation of human pathogenic influenza viruses.

CONCLUSION:

Rubini elderberry liquid extract is active against human pathogenic bacteria as well as influenza viruses. The activities shown suggest that additional and alternative approaches to combat infections might be provided by this natural product.

PMID:

21352539

[PubMed - indexed for MEDLINE]

PMCID: PMC3056848

Free PMC Article

 

 

Phytother Res. 2010 Jan;24(1):1-8.

A systematic review on the sambuci fructus effect and efficacy profiles.

Vlachojannis JE, Cameron M, Chrubasik S.

Source

Department of Orthodontics, Columbia University, 630 W 168th, NYC, NY 10032, USA. jec2142@columbia.edu

Abstract

The berries of European elder are used in traditional German medicine for various complaints. Due to insufficient research data, elderberry fruit was not monographed by the German Commission E at the end of the last century. A comprehensive review of the literature was conducted to summarize the pharmacological and clinical effects of elderberry fruit. Several databases and other sources were searched to identify in vitro and animal studies, and clinical trials investigating elderberry fruit preparations. For the latter, the level of evidence was evaluated as described previously. Elderberry fruit preparations may provide antioxidant, antiviral and antiproliferative effects in vitro. One animal experiment and one clinical trial were able to back the antioxidative impact in terms of a weak antilipidemic effect. Antibacterial and antiinflammatory effects seem possible, but need further support. In rats, an aqueous elderberry fruit extract produced central depression and analgesia and an ethanol fruit extract improved acetic acid-induced colitis. Several in vitro studies together with two exploratory studies in humans and one open study in chimpanzees indicate that the aqueous elderberry extract Sambucol may be useful for the treatment of viral influenza infections. These promising effects of elderberry fruit preparations from experimental and clinical studies should be backed by more rigorous studies before these preparations are recommended in the prevention of diseases and in treatment schedules.

(c) 2009 John Wiley & Sons, Ltd.

PMID:

19548290

 

 

Altern Med Rev. 2007 Mar;12(1):25-48.

Colds and influenza: a review of diagnosis and conventional, botanical, and nutritional considerations.

Roxas M, Jurenka J.

Source

Thorne Research, PO Box 25, Dover, ID 83825, USA. m.roxas@comcast.net

Abstract

The common cold is the leading cause of doctor visits in the United States and annually results in 189 million lost school days. In the course of one year the U.S. population contracts approximately 1 billion colds. Influenza infection is still a leading cause of morbidity and mortality, accounting for 20-25 million doctor visits and 36,000 deaths per year in the United States. Conventional therapies for colds and flu focus primarily on temporary symptom relief and include over-the-counter antipyretics, anti-inflammatories, and decongestants. Treatment for influenza also includes prescription antiviral agents and vaccines for prevention. This article reviews the common cold and influenza viruses, presents the conventional treatment options, and highlights select botanicals (Echinacea spp., Sambucus nigra, larch arabinogalactan, Astragalus membranaceous, Baptisia tinctoria, Allium sativa, Panax quinquefolium, Eleutherococcus senticosus, Andrographis paniculata, olive leaf extract, and Isatis tinctoria) and nutritional considerations (vitamins A and C, zinc, high lactoferrin whey protein, N-acetylcysteine, and DHEA) that may help in the prevention and treatment of these conditions.

 

J Altern Complement Med. 2000 Aug;6(4):327-34.

The efficacy of echinacea compound herbal tea preparation on the severity and duration of upper respiratory and flu symptoms: a randomized, double-blind placebo-controlled study.

Lindenmuth GF, Lindenmuth EB.

Source

Rest Haven-York, York College of Pennsylvania, USA.

Abstract

OBJECTIVES:

The aim of this study was to determine the efficacy of an echinacea compound herbal tea preparation (Echinacea Plus) given at early onset of cold or flu symptoms in a random assignment double-blind placebo-controlled study.

DESIGN AND SUBJECTS:

A total of 95 subjects with early symptoms of cold or flu (runny nose, scratchy throat, fever) were randomly assigned to receive Echinacea Plus tea five to six cups per day titrating to 1 over 5 days or placebo in a double-blind situation. Each participant completed a questionnaire 14 days after beginning the program. The efficacy, number of days the symptoms lasted, and number of days for change were measured with a self scoring questionnaire.

RESULTS:

The study period was 90 days (January 1, 1999 to March 30, 1999). There was a significant difference between the experimental group (Echinacea Plus) and control group (placebo) for all 3 questions measured: p < 0.001. There were no negative effects reported by any of the subjects in either group.

CONCLUSIONS:

Treatment with Echinacea Plus tea at early onset of cold or flu symptoms was effective for relieving these symptoms in a shorter period of time than a placebo.

 

Nutr J. 2010 Aug 26;9:32.

Proprietary arabinogalactan extract increases antibody response to the pneumonia vaccine: a randomized, double-blind, placebo-controlled, pilot study in healthy volunteers.

Udani JK, Singh BB, Barrett ML, Singh VJ.

Source

Medicus Research LLC, Northridge, CA 91325, USA. jay.udani@medicusresearch.com

Abstract

BACKGROUND:

Arabinogalactan from Larch tree (Larix spp.) bark has previously demonstrated immunostimulatory activity. The purpose of this study was to test the hypothesis that ingestion of a proprietary arabinogalactan extract, ResistAid™, would selectively enhance the antibody response to the pneumococcal (pneumonia) vaccine in healthy adults.

METHODS:

This randomized, double-blind, placebo-controlled, parallel group pilot study included 45 healthy adults who had not previously been vaccinated against Streptococcus pneumoniae. The volunteers began taking the study product or placebo (daily dosage 4.5 g) at the screening visit (V1-Day 0) and continued over the entire 72 day study period. After 30 days the subjects received the 23-valent pneumococcal vaccine (V2). They were monitored the following day (V3-Day 31), as well as 21 days (V4-Day 51) and 42 days (V5-Day 72) after vaccination. Responses by the adaptive immune system (antigen specific) were measured via pneumococcal IgG antibodies (subtypes 4, 6B, 9V, 14, 18C, 19F, and 23F) and salivary IgA levels. Responses by the innate immune system (non-specific) were measured via white blood cell counts, inflammatory cytokines and the complement system.

RESULTS:

Vaccination significantly increased pneumococcal IgG levels as expected. The arabinogalactan group demonstrated a statistically significant greater IgG antibody response than the placebo group in two antibodies subtypes (18C and 23F) at both Day 51 (p = 0.006 and p = 0.002) and at Day 72 (p = 0.008 and p = 0.041). These same subtypes (18C and 23F) also demonstrated change scores from baseline which were significant, in favor of the arabinogalactan group, at Day 51 (p = 0.033 and 0.001) and at Day 72 (p = 0.012 and p = 0.003). Change scores from baseline and mean values were greater in the arabinogalactan group than placebo for most time points in antibody subtypes 4, 6B, 9V, and 19F, but these differences did not reach statistical significance. There was no effect from the vaccine or arabinogalactan on salivary IgA, white blood cell count, inflammatory cytokines or complement.

CONCLUSIONS:

The proprietary arabinogalactan extract (ResistAid), tested in this randomized, double-blind, placebo-controlled, parallel-group pilot study, increased the antibody response of healthy volunteers to the 23-valent pneumococcal vaccine compared to placebo.

TRIAL REGISTRATION:

ISRCTN98817459.

 

Ter Arkh. 2003;75(3):53-6.

[Effect of long-acting garlic tablets "allicor" on the incidence of acute respiratory viral infections in children].

[Article in Russian]

Andrianova IV, Sobenin IA, Sereda EV, Borodina LI, Studenikin MI.

Abstract

AIM:

To elucidate the prospects administration of allicor (long-releasing garlic tablets) in prevention of acute respiratory diseases (ARD) in children vs benzimidazole (dibazole).

MATERIAL AND METHODS:

At the first stage, tolerance of allicor (600 mg/day) and its effects on ARD morbidity were investigated in an opened 5-month study in 172 children aged 7-16 years compared to 468 controls. As the second stage, the effects of allicor (300 mg/day) on ASRD morbidity were investigated in a double-blind placebo-controlled randomized 5-month trial in 42 children aged 10-12 years in comparison with 41 placebo-treated children and 73 benzimidazole-treated children.

RESULTS:

At the first stage of the study allicor was not observed to induce gastrointestinal side effects in children at any dosage while ARD morbidity was reduced 2-4-fold as compared to the controls. At the second stage of the study allicor reduced ARD morbidity 1.7-fold compared to placebo and 2.4-fold vs benzimidazole. There was no significant difference in ARD morbidity between placebo- and benzimidazole-treated groups. Health index in allicor-treated group was 1.5-fold higher as compared either to placebo- or benzimidazole-treated children.

CONCLUSION:

Thus, the results of this study have demonstrated that allicor is effective for non-specific prevention of acute respiratory infections in children and has no side effects. ARD prevention with benzimidazole appeared ineffective in placebo-controlled study, so the development of new useful and safe preparations is of ultimate importance.

 

Drugs Exp Clin Res. 1996;22(2):65-72.

Efficacy and safety of the standardised Ginseng extract G115 for potentiating vaccination against the influenza syndrome and protection against the common cold [corrected].

Scaglione F, Cattaneo G, Alessandria M, Cogo R.

Source

Department of Pharmacology, University of Milan, Italy.

Erratum in

  • Drugs Exp Clin Res 1996;22(6):338.

Abstract

The aim of the study was to determine the properties of a standardized extract of ginseng root in inducing a higher immune response in vaccination against influenza. Attention was also paid to the common cold in this multicentre, two-arm, randomized, placebo-controlled, double-blind investigation. A total of 227 volunteers who visited 3 private practices in Milan received daily oral capsule doses of either placebo (113) or 100 mg of standardized ginseng extract Ginsana G 115 (114) for a period of 12 weeks within which they received an anti-influenza polyvalent vaccination at week 4. As a result, while the frequency of influenza or common cold between weeks 4 and 12 was 42 cases in the placebo group, it was only 15 cases in the G115 group, the difference being statistically highly significant (p < 0.001). Whereas antibody titres by week 8 rose to an average of 171 units in the placebo group, they rose to an average of 272 units in the G115 group (p < 0.0001). Natural killer (NK) activity levels at weeks 8 and 12 were nearly twice as high in the G115 group as compared to the placebo group (p < 0.0001). In all the volunteers, laboratory values of 24 safety parameters showed no significant differences between the end and the beginning of the 12-week study in either of the groups. There were only 9 adverse events in the study, the principal one being insomnia.

 

J Am Geriatr Soc. 2004 Jan;52(1):13-9.

A placebo-controlled trial of a proprietary extract of North American ginseng (CVT-E002) to prevent acute respiratory illness in institutionalized older adults.

McElhaney JE, Gravenstein S, Cole SK, Davidson E, O'neill D, Petitjean S, Rumble B, Shan JJ.

Source

Eastern Virginia Medical School, Norfolk, Virginia, USA. jmcelhaney@uchc.edu

Erratum in

  • J Am Geriatr Soc. 2004 May;52(5):following 856.

Abstract

OBJECTIVES:

To compare a proprietary extract of American ginseng, CVT-E002, with placebo in preventing acute respiratory illness (ARI) in an institutional setting during the influenza season.

DESIGN:

Two randomized, double-blind, placebo-controlled trials conducted late in the 2000 (8 week) and 2000-2001 (12 week) influenza seasons.

SETTING:

Long-term care setting that included nursing home and assisted living at three sites.

PARTICIPANTS:

Eighty-nine (2000) and 109 (2000-2001) enrolled subjects, average age 81 and 83.5, respectively; 74% women. Approximately 90% had received influenza vaccine in each of the 2 years.

INTERVENTION:

Oral twice-daily administration of a proprietary ginseng extract, CVT-E002, 200 mg or placebo.

MEASUREMENTS:

ARI was defined as two new respiratory symptoms or one with a constitutional symptom. Confirmation of viral ARI was by culture (influenza or respiratory syncytial virus (RSV)) or serology for influenza. Laboratory safety monitoring was done at 0, 4, and 8 or 12 weeks.

RESULTS:

An intent-to-treat analysis of pooled data corrected for drug exposure time showed that the incidence of laboratory-confirmed influenza illness (LCII) was greater in placebo- (7 cases/101 subjects) than CVT-E002-treated (1/97) groups (odds ratio (OR)=7.73, P=.033). Combined data for LCII and RSV illness were also greater in placebo- (9/101) than CVT-E002-treated (1/97) groups (OR=10.50, P=.009), for an overall 89% relative risk reduction of ARI in the CVT-E002 group.

CONCLUSION:

CVT-E002 was shown to be safe, well tolerated, and potentially effective for preventing ARI due to influenza and RSV.

PMID:

14687309

[PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/14687309

 

 

CMAJ. 2005 Oct 25;173(9):1043-8.

Efficacy of an extract of North American ginseng containing poly-furanosyl-pyranosyl-saccharides for preventing upper respiratory tract infections: a randomized controlled trial.

Predy GN, Goel V, Lovlin R, Donner A, Stitt L, Basu TK.

Source

Capital Health, Edmonton, Alta.

Abstract

BACKGROUND:

Upper respiratory tract infections are a major source of morbidity throughout the world. Extracts of the root of North American ginseng (Panax quinquefolium) have been found to have the potential to modulate both natural and acquired immune responses. We sought to examine the efficacy of an extract of North American ginseng root in preventing colds.

METHODS:

We conducted a randomized, double-blind, placebo-controlled study at the onset of the influenza season. A total of 323 subjects 18-65 years of age with a history of at least 2 colds in the previous year were recruited from the general population in Edmonton, Alberta. The participants were instructed to take 2 capsules per day of either the North American ginseng extract or a placebo for a period of 4 months. The primary outcome measure was the number of Jackson-verified colds. Secondary variables measured included symptom severity, total number of days of symptoms and duration of all colds. Cold symptoms were scored by subjects using a 4-point scale.

RESULTS:

Subjects who did not start treatment were excluded from the analysis (23 in the ginseng group and 21 in the placebo group), leaving 130 in the ginseng group and 149 in the placebo group. The mean number of colds per person was lower in the ginseng group than in the placebo group (0.68 [standard deviation (SD) 0.82] v. 0.93 [SD 0.91], difference 0.25%, 95% confidence interval [CI] 0.04-0.45). The proportion of subjects with 2 or more Jackson-verified colds during the 4-month period (10.0% v. 22.8%, 12.8% difference, 95% CI 4.3-21.3) was significantly lower in the ginseng group than in the placebo group, as were the total symptom score (77.5 [SD 84.6] v. 112.3 [SD 102.5], difference 1.5%, 95% CI 1.2-2.0) and the total number of days cold symptoms were reported (10.8 [SD 9.7] v. 16.5 [SD 13.8] days, difference 1.6%, 95% CI 1.3-2.0) for all colds.

INTERPRETATION:

Ingestion of a poly-furanosyl-pyranosyl-saccharide-rich extract of the roots of North American ginseng in a moderate dose over 4 months reduced the mean number of colds per person, the proportion of subjects who experienced 2 or more colds, the severity of symptoms and the number of days cold symptoms were reported.

 

J Altern Complement Med. 2006 Mar;12(2):153-7.

Efficacy of COLD-fX in the prevention of respiratory symptoms in community-dwelling adults: a randomized, double-blinded, placebo controlled trial.

McElhaney JE, Goel V, Toane B, Hooten J, Shan JJ.

Source

Center for Immunotherapy of Cancer and Infectious Diseases, School of Medicine, University of Connecticut, Farmington, CT, USA.

Abstract

BACKGROUND:

COLD-fX (CVT-E002), a proprietary extract of the roots of North American ginseng (Panax quinquefolium), rich in poly-furanosyl-pyranosyl-saccharides, has been found efficacious in the prevention of respiratory infections in institutionalized seniors and healthy adults.

OBJECTIVE:

We examined the efficacy of COLD-fX in the prevention of acute respiratory illness (ARI) in community dwelling seniors.

DESIGN:

This was a randomized, double-blind, placebo controlled trial.

INTERVENTION:

The participants were asked to take 2 capsules/day of either COLD-fX or placebo (200 mg/ capsule) for a period of 4 months.

SUBJECTS:

A total of 43 community-dwelling adults aged 65 years or older were recruited. Following one month of intervention, subjects were immunized with influenza vaccine.

OUTCOME MEASURES:

Subjects recorded the incidence and duration of respiratory symptoms during the study. They also recorded the incidence of adverse events during the study.

RESULTS:

The frequency and duration of ARI during the first two months of the study was found to be similar in the two groups. However, during the last 2 months (November and December) significantly fewer subjects in the COLD-fX group 32% reported ARI compared to the placebo group 62%. The duration of symptoms during the last 2 months was significantly shorter in the COLD-fX group than the placebo group (5.6 days in the COLD-fX group vs 12.6 days in the placebo group). There was no influenza illness circulating in the community during the period of the study.

CONCLUSIONS:

Ingestion of COLD-fX by immunocompetent seniors during an early "cold and flu" season reduced the relative risk and duration of respiratory symptoms by 48% and 55%, respectively. Daily COLD-fX administration can thus be a safe, natural therapeutic means for the prevention of ARI in healthy seniors.

PMID:

16566675

 

J Ethnopharmacol. 2011 Oct 11;137(3):1542-6. Epub 2011 Aug 22.

Dual functions of ginsenosides in protecting human endothelial cells against influenza H9N2-induced inflammation and apoptosis.

Chan LY, Kwok HH, Chan RW, Peiris MJ, Mak NK, Wong RN, Chan MC, Yue PY.

Source

Department of Biology, Faculty of Science, Hong Kong Baptist University, Kowloon Tong, Hong Kong SAR, China.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE:

Panax ginseng is a precious traditional Chinese herbal medicine which has been utilized as herbal tonic for improving immunity. The active component, ginsenosides have been shown to possess various pharmacological functions including immunomodulation and cardiovascular protection.

AIM OF THE STUDY:

To investigate the immunomodulatory effect and anti-apoptotic effect of ginsenosides on avian influenza-infected human endothelial cells, and to present evidence for the cardiovascular protection by ginseng during influenza infection.

MATERIALS AND METHODS:

Human umbilical vein endothelial cells (HUVECs) were infected with avian influenza H9N2/G1 to induce IP-10 production and cell death, cells were then incubated with ginsenosides PPT and Re. The level of IP-10 and microRNA was determined by ELISA and real-time PCR respectively. Cell death was determined by MTT, TUNEL and flow cytometry.

RESULTS:

Ginsenoside metabolite protopanaxatriol showed significant suppression effect on IP-10 production upon H9N2/G1 infection through up-regulation of miR-15b expression. In addition, ginsenoside-induced cytoprotection was reflected in the increase of cell viability. Data from flow cytometry analysis and TUNEL assay also showed that ginsenoside Re could protect ECs from H9N2/G1-induced apoptosis and DNA damage.

CONCLUSIONS:

This report further supports the traditional belief for immunomodulatory effects of ginseng, also demonstrated the partial protective mechanism of ginsenosides on avian influenza infection and its related endothelial dysfunction.

Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

 

Virol J. 2008 Feb 25;5:29.

On the epidemiology of influenza.

Cannell JJ, Zasloff M, Garland CF, Scragg R, Giovannucci E.

Source

Department of Psychiatry, Atascadero State Hospital, 10333 El Camino Real, Atascadero, CA 93423, USA. jcannell@ash.dmh.ca.gov

Abstract

The epidemiology of influenza swarms with incongruities, incongruities exhaustively detailed by the late British epidemiologist, Edgar Hope-Simpson. He was the first to propose a parsimonious theory explaining why influenza is, as Gregg said, "seemingly unmindful of traditional infectious disease behavioral patterns." Recent discoveries indicate vitamin D upregulates the endogenous antibiotics of innate immunity and suggest that the incongruities explored by Hope-Simpson may be secondary to the epidemiology of vitamin D deficiency. We identify - and attempt to explain - nine influenza conundrums: (1) Why is influenza both seasonal and ubiquitous and where is the virus between epidemics? (2) Why are the epidemics so explosive? (3) Why do they end so abruptly? (4) What explains the frequent coincidental timing of epidemics in countries of similar latitude? (5) Why is the serial interval obscure? (6) Why is the secondary attack rate so low? (7) Why did epidemics in previous ages spread so rapidly, despite the lack of modern transport? (8) Why does experimental inoculation of seronegative humans fail to cause illness in all the volunteers? (9) Why has influenza mortality of the aged not declined as their vaccination rates increased? We review recent discoveries about vitamin D's effects on innate immunity, human studies attempting sick-to-well transmission, naturalistic reports of human transmission, studies of serial interval, secondary attack rates, and relevant animal studies. We hypothesize that two factors explain the nine conundrums: vitamin D's seasonal and population effects on innate immunity, and the presence of a subpopulation of "good infectors." If true, our revision of Edgar Hope-Simpson's theory has profound implications for the prevention of influenza.

18298852

 

 

Int J Infect Dis. 2010 Dec;14(12):e1099-105. Epub 2010 Oct 29.

The seasonality of pandemic and non-pandemic influenzas: the roles of solar radiation and vitamin D.

Juzeniene A, Ma LW, Kwitniewski M, Polev GA, Lagunova Z, Dahlback A, Moan J.

Source

Department of Radiation Biology, Institute for Cancer Research, the Norwegian Radium Hospital, Oslo University Hospital, Montebello, N-0310 Oslo, Norway. asta.juzeniene@rr-research.no

Abstract

OBJECTIVES:

Seasonal variations in ultraviolet B (UVB) radiation cause seasonal variations in vitamin D status. This may influence immune responses and play a role in the seasonality of influenza.

METHODS:

Pandemic and non-pandemic influenzas in Sweden, Norway, the USA, Singapore, and Japan were studied. Weekly/monthly influenza incidence and death rates were evaluated in view of monthly UVB fluences.

RESULTS:

Non-pandemic influenzas mostly occur in the winter season in temperate regions. UVB calculations show that at high latitudes very little, if any, vitamin D is produced in the skin during the winter. Even at 26°N (Okinawa) there is about four times more UVB during the summer than during the winter. In tropical regions there are two minor peaks in vitamin D photosynthesis, and practically no seasonality of influenza. Pandemics may start with a wave in an arbitrary season, while secondary waves often occur the following winter. Thus, it appears that a low vitamin D status may play a significant role in most influenzas.

CONCLUSIONS:

In temperate latitudes even pandemic influenzas often show a clear seasonality. The data support the hypothesis that high fluences of UVB radiation (vitamin D level), as occur in the summer, act in a protective manner with respect to influenza.

Copyright © 2010 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

PMID:

21036090

 

Mol Nutr Food Res. 2011 Jan;55(1):96-108. doi: 10.1002/mnfr.201000174. Epub 2010 Sep 7.

A review of the critical role of vitamin D in the functioning of the immune system and the clinical implications of vitamin D deficiency.

Schwalfenberg GK.

Source

University of Alberta, Edmonton, Alberta, Canada. schwalfe@ualberta.ca

Abstract

This review looks at the critical role of vitamin D in improving barrier function, production of antimicrobial peptides including cathelicidin and some defensins, and immune modulation. The function of vitamin D in the innate immune system and in the epithelial cells of the oral cavity, lung, gastrointestinal system, genito-urinary system, skin and surface of the eye is discussed. Clinical conditions are reviewed where vitamin D may play a role in the prevention of infections or where it may be used as primary or adjuvant treatment for viral, bacterial and fungal infections. Several conditions such as tuberculosis, psoriasis, eczema, Crohn's disease, chest infections, wound infections, influenza, urinary tract infections, eye infections and wound healing may benefit from adequate circulating 25(OH)D as substrate. Clinical diseases are presented in which optimization of 25(OH)D levels may benefit or cause harm according to present day knowledge. The safety of using larger doses of vitamin D in various clinical settings is discussed.

Copyright © 2011 WI

 

 

Vitam Horm. 2011;86:217-37.

Vitamin D effects on lung immunity and respiratory diseases.

Hansdottir S, Monick MM.

Source

Department of Medicine, University of Iowa Carver College of Medicine and Veterans Administration Medical Center, Iowa City, Iowa, USA.

Abstract

Our understanding of vitamin D metabolism and biological effects has grown exponentially in recent years and it has become clear that vitamin D has extensive immunomodulatory effects. The active vitamin D generating enzyme, 1α-hydroxylase, is expressed by the airway epithelium, alveolar macrophages, dendritic cells, and lymphocytes indicating that active vitamin D can be produced locally within the lungs. Vitamin D generated in tissues is responsible for many of the immunomodulatory actions of vitamin D. The effects of vitamin D within the lungs include increased secretion of the antimicrobial peptide cathelicidin, decreased chemokine production, inhibition of dendritic cell activation, and alteration of T-cell activation. These cellular effects are important for host responses against infection and the development of allergic lung diseases like asthma. Epidemiological studies do suggest that vitamin D deficiency predisposes to viral respiratory tract infections and mycobacterial infections and that vitamin D may play a role in the development and treatment of asthma. Randomized, placebo-controlled trials are lacking but ongoing.

Copyright © 2011 Elsevier Inc. All rights reserved.

 

 

Am J Clin Nutr. 2010 May;91(5):1255-60. Epub 2010 Mar 10.

Randomized trial of vitamin D supplementation to prevent seasonal influenza A in schoolchildren.

Urashima M, Segawa T, Okazaki M, Kurihara M, Wada Y, Ida H.

Source

Division of Molecular Epidemiology, Jikei University School of Medicine, Nishi-shimbashi 3-25-8, Minato-ku, Tokyo 105-8461, Japan. urashima@jikei.ac.jp

Abstract

BACKGROUND:

To our knowledge, no rigorously designed clinical trials have evaluated the relation between vitamin D and physician-diagnosed seasonal influenza.

OBJECTIVE:

We investigated the effect of vitamin D supplements on the incidence of seasonal influenza A in schoolchildren.

DESIGN:

From December 2008 through March 2009, we conducted a randomized, double-blind, placebo-controlled trial comparing vitamin D(3) supplements (1200 IU/d) with placebo in schoolchildren. The primary outcome was the incidence of influenza A, diagnosed with influenza antigen testing with a nasopharyngeal swab specimen.

RESULTS:

Influenza A occurred in 18 of 167 (10.8%) children in the vitamin D(3) group compared with 31 of 167 (18.6%) children in the placebo group [relative risk (RR), 0.58; 95% CI: 0.34, 0.99; P = 0.04]. The reduction in influenza A was more prominent in children who had not been taking other vitamin D supplements (RR: 0.36; 95% CI: 0.17, 0.79; P = 0.006) and who started nursery school after age 3 y (RR: 0.36; 95% CI: 0.17, 0.78; P = 0.005). In children with a previous diagnosis of asthma, asthma attacks as a secondary outcome occurred in 2 children receiving vitamin D(3) compared with 12 children receiving placebo (RR: 0.17; 95% CI: 0.04, 0.73; P = 0.006).

CONCLUSION:

This study suggests that vitamin D(3) supplementation during the winter may reduce the incidence of influenza A, especially in specific subgroups of schoolchildren. This trial was registered at https://center.umin.ac.jp as UMIN000001373.

PMID:

20219962

[PubMed - indexed for MEDLINE]

Free full

 

Scand J Infect Dis. 2011 Oct 25. [Epub ahead of print]

Vitamin D supplementation did not prevent influenza-like illness as diagnosed retrospectively by questionnaires in subjects participating in randomized clinical trials.

Jorde R, Witham M, Janssens W, Rolighed L, Borchhardt K, Boer IH, Grimnes G, Hutchinson MS.

Source

Endocrinology Research Group, Institute of Clinical Medicine, University of Tromsø, and Medical Clinic, University Hospital of North Norway , Tromsø , Norway.

Abstract

Abstract Background: Vitamin D deficiency has been associated with a number of diseases, including influenza. Whether or not this reflects a causal relationship is unknown. We therefore wanted to examine if supplementation with vitamin D would affect the incidence and severity of influenza-like disease. Methods: Questionnaires on influenza were sent to subjects participating in ongoing placebo-controlled intervention studies with vitamin D supplementation, up until the end of April 2010. Results: Five hundred and sixty-nine subjects from 10 different clinical trials were included in the study, of whom 289 were randomized to receive vitamin D (1111-6800 IU/day) and 280 to receive placebo. Influenza-like disease during the previous fall/winter was reported in 38 subjects in the vitamin D group and 42 in the placebo group (non-significant), of whom 25 and 26 subjects, respectively, fulfilled our clinical criteria for influenza. In these latter subjects, the duration of illness was significantly longer among those in the vitamin D group than among those in the placebo group (median 7 (range 2-60) days vs median 4 (range 2-18) days; p = 0.007). However, this difference was not statistically significant if all 38 (vitamin D) and 42 (placebo) subjects who reported symptoms were included. Conclusion: Our results do not support the hypothesis that high doses of vitamin D supplementation will have a pronounced effect on influenza-like disease in populations not targeted for high influenza risk.

PMID:

22026455

[PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov/pubmed/22026455

 

Curr Med Res Opin. 2010 Jun;26(6):1413-22.

Efficacy and tolerability of EPs 7630 tablets in patients with acute bronchitis: a randomised, double-blind, placebo-controlled dose-finding study with a herbal drug preparation from Pelargonium sidoides.

Matthys H, Lizogub VG, Malek FA, Kieser M.

Source

Department of Pneumology, University Hospital Freiburg, Freiburg, Germany. hmatthys@t-online.de

Abstract

OBJECTIVE:

Acute bronchitis is one of the most frequent health complaints for which patients seek medical advice. Although viral infections prevail, antibiotics are commonly prescribed. In this study, the efficacy and tolerability of EPs 7630 tablets, a herbal drug preparation from the roots of Pelargonium sidoides, were investigated in adults with acute bronchitis outside the strict indication for antibiotics.

RESEARCH DESIGN AND METHODS:

In this randomised, double-blind, placebo-controlled, multicentre dose-finding trial using an adaptive group-sequential design, 406 patients were randomly assigned to one of four parallel treatment groups (10 mg EPs 7630 tablets three times a day (30-mg group), 20 mg EPs 7630 tablets three times a day (60-mg group), 30 mg EPs 7630 tablets three times a day (90-mg group) or placebo three times a day) for a treatment period of 7 days. Primary endpoint was the change in the total score of bronchitis-specific symptoms (BSS) from baseline to day 7.

RESULTS:

Between day 0 and day 7, the mean BSS score decreased by 2.7 +/- 2.3 (placebo), 4.3 +/- 1.9 (30-mg group), 6.1 +/- 2.1 (60-mg group), and 6.3 +/- 2.0 points (90-mg group), respectively. The differences between the EPs 7630 groups and placebo were statistically significant (p < 0.0001, each). The secondary endpoints showed comparable results. EPs 7630 was well-tolerated. All documented adverse events were of mild to moderate intensity; their frequency was dose-dependent. No serious adverse events were reported.

CONCLUSION:

This study demonstrated statistically significant and clinically relevant superiority of all three tested dosages of EPs 7630 over placebo. All dosages of EPs 7630 were well-tolerated. Taking into account both efficacy and safety, the results of this study indicate that the 20 mg tablets of EPs 7630 taken three times daily constitute the optimal dose with respect to the benefit-risk ratio.

PMID:

20387996

 

 

Int J Clin Pharmacol Ther. 2010 Mar;48(3):184-91.

Efficacy and tolerability of EPs 7630 in children and adolescents with acute bronchitis - a randomized, double-blind, placebo-controlled multicenter trial with a herbal drug preparation from Pelargonium sidoides roots.

Kamin W, Maydannik V, Malek FA, Kieser M.

Source

University Hospital Pediatrics, Mainz, Germany. wkamin@evkhamm.de

Abstract

OBJECTIVE:

The study aim was to demonstrate the efficacy and to investigate the tolerability of EPs 7630, a herbal drug preparation from Pelargonium sidoides roots, in the treatment of patients (1 - 18 years) with acute bronchitis outside the strict indication for antibiotics.

MATERIALS AND METHODS:

A total of 200 patients were randomized to receive either active drug containing EPs 7630 (1 - 6 years: 3 x 10 drops/d; > 6 - 12 years: 3 x 20 drops/d; > 12 - 18 years: 3 x 30 drops/d) or placebo for 7 consecutive days. Primary outcome measure: change in the total score of bronchitis-specific symptoms (BSS) from Day 0 to Day 7. Main secondary outcome measures: treatment outcome, patients' satisfaction with treatment, onset of effect, bed rest.

RESULTS:

From baseline to Day 7, the mean BSS score improved significantly more for EPs 7630 compared with placebo (3.4 +/- 1.8 vs. 1.2 +/- 1.8 points, p < 0.0001). On Day 7, treatment outcome was significantly better (p < 0.0001), satisfaction with treatment more pronounced (77.6% vs. 25.8%, p < 0.0001), onset of effect faster, and time of bed rest shorter as compared with placebo. Tolerability was similarly good in both groups. All adverse events were assessed as non-serious.

CONCLUSION:

EPs 7630 was shown to be efficacious and safe in the treatment of acute bronchitis in children and adolescents outside the strict indication for antibiotics with patients treated with EPs 7630 perceiving a more favorable course of the disease and a good tolerability as compared with placebo.

PMID:

20197012

 

Pelargonium sidoides in acute bronchitis - Health-related quality of life and patient-reported outcome in adults receiving EPs 7630 treatment].

Matthys H, Lizogub VG, Funk P, Malek FA.

Wien Med Wochenschr. 2010 Dec;160(21-22):564-70. German.

PMID:

 

Efficacy and tolerability of EPs 7630 in patients (aged 6-18 years old) with acute bronchitis.

Kamin W, Maydannik VG, Malek FA, Kieser M.

Acta Paediatr. 2010 Apr;99(4):537-43. Epub 2010 Jan 11.

PMID:

20070280

 

Efficacy and tolerability of EPs 7630 in patients (aged 6-18 years old) with acute bronchitis.

Kamin W, Maydannik VG, Malek FA, Kieser M.

Acta Paediatr. 2010 Apr;99(4):537-43. Epub 2010 Jan 11.

PMID:

20070280

 

EPs 7630 improves acute bronchitic symptoms and shortens time to remission. Results of a randomised, double-blind, placebo-controlled, multicentre trial.

Matthys H, Funk P.

Planta Med. 2008 May;74(6):686-92. Epub 2008 Apr 30.

 

Efficacy of a pelargonium sidoides preparation in patients with the common cold: a randomized, double blind, placebo-controlled clinical trial.

Lizogub VG, Riley DS, Heger M.

Explore (NY). 2007 Nov-Dec;3(6):573-84.

PMID:

18005909

 

Treatment of acute bronchitis with a liquid herbal drug preparation from Pelargonium sidoides (EPs 7630): a randomised, double-blind, placebo-controlled, multicentre study.

Matthys H, Heger M.

Curr Med Res Opin. 2007 Feb;23(2):323-31.

PMID:

17288687

 

Treatment of acute rhinosinusitis with the preparation from Pelargonium sidoides EPs 7630: a randomized, double-blind, placebo-controlled trial.

Bachert C, Schapowal A, Funk P, Kieser M.

Rhinology. 2009 Mar;47(1):51-8.

PMID:

19382496

 

Liquid herbal drug preparation from the root of Pelargonium sidoides is effective against acute bronchitis: results of a double-blind study with 124 patients.

Schulz V.

Phytomedicine. 2007;14 Suppl 6:74-5. Epub 2007 Feb 2. No abstract available.

PMID:

17276048

[PubMed - indexed for MEDLINE]

Related citations

 10.

EPs 7630-solution--an effective therapeutic option in acute and exacerbating bronchitis.

Matthys H, Heger M.

Phytomedicine. 2007;14 Suppl 6:65-8. Epub 2006 Dec 20.

PMID:

17184984

[PubMed - indexed for MEDLINE]

Related citations

 11.

Pelargonium sidoides preparation (EPs 7630) in the treatment of acute bronchitis in adults and children.

Matthys H, Kamin W, Funk P, Heger M.

Phytomedicine. 2007;14 Suppl 6:69-73. Epub 2006 Dec 20.

PMID:

17184981

[PubMed - indexed for MEDLINE]

Related citations

 12.

Treatment of acute bronchitis in adults with a pelargonium sidoides preparation (EPs 7630): a randomized, double-blind, placebo-controlled trial.

Chuchalin AG, Berman B, Lehmacher W.

Explore (NY). 2005 Nov;1(6):437-45.

PMID:

16781588

[PubMed - indexed for MEDLINE]

Related citations

 13.

Efficacy of extract of Pelargonium sidoides in children with acute non-group A beta-hemolytic streptococcus tonsillopharyngitis: a randomized, double-blind, placebo-controlled trial.

Bereznoy VV, Riley DS, Wassmer G, Heger M.

Altern Ther Health Med. 2003 Sep-Oct;9(5):68-79.

PMID:

14526713

[PubMed - indexed for MEDLINE]

Related citations

 14.

Efficacy and safety of an extract of Pelargonium sidoides (EPs 7630) in adults with acute bronchitis. A randomised, double-blind, placebo-controlled trial.

Matthys H, Eisebitt R, Seith B, Heger M.

Phytomedicine. 2003;10 Suppl 4:7-17.

PMID:

12807337

[PubMed - indexed for MEDLINE]

Related citations

 

Treatment of acute bronchitis with a liquid herbal drug preparation from Pelargonium sidoides (EPs 7630): a randomised, double-blind, placebo-controlled, multicentre study.

Matthys H, Heger M.

Curr Med Res Opin. 2007 Feb;23(2):323-31.

PMID:

17288687

[PubMed - indexed for MEDLINE]

 

Phytomedicine. 2011 Mar 15;18(5):384-6. Epub 2010 Oct 30.

Investigation of the influence of EPs® 7630, a herbal drug preparation from Pelargonium sidoides, on replication of a broad panel of respiratory viruses.

Michaelis M, Doerr HW, Cinatl J Jr.

Source

Institut für Medizinische Virologie, Klinikum der JW Goethe-Universität, Frankfurt am Main, Germany.

Abstract

The Pelargonium sidoides extract EPs® 7630 is an approved drug for the treatment of acute bronchitis in Germany. The postulated mechanisms underlying beneficial effects of EPs® 7630 in bronchitis patients include immunomodulatory and cytoprotective effects, inhibition of interaction between bacteria and host cells, and increase of cilliary beat frequency on respiratory cells. Here, we investigated the influence of EPs® 7630 on replication of a panel of respiratory viruses. Determination of virus-induced cytopathogenic effects and virus titres revealed that EPs® 7630 at concentrations up to 100 μg/ml interfered with replication of seasonal influenza A virus strains (H1N1, H3N2), respiratory syncytial virus, human coronavirus, parainfluenza virus, and coxsackie virus but did not affect replication of highly pathogenic avian influenza A virus (H5N1), adenovirus, or rhinovirus. Therefore, antiviral effects may contribute to the beneficial effects exerted by EPs® 7630 in acute bronchitis patients.

Copyright © 2010 Elsevier GmbH. All rights reserved.

PMID:

21036571

 

 

Phytomedicine. 2007;14 Suppl 6:27-31. Epub 2006 Dec 19.

Inhibition of lipopolysaccharid-induced sickness behavior by a dry extract from the roots of Pelargonium sidoides (EPs 7630) in mice.

Nöldner M, Schötz K.

Source

Department of Preclinical Research, Dr. Willmar Schwabe GmbH & Co.KG, Willmar Schwabe Str. 4, D-76227 Karlsruhe, Germany. michael.noeldner@schwabe.de <michael.noeldner@schwabe.de>

Abstract

The host response to infections comprise the synthesis and release of proinflammatory cytokines (e.g. IL-1ss, TNF-alpha, IL-6) which induce symptoms of sickness behavior characterised by anorexia, depressed activity, listlessness or malaise. In laboratory animals, sickness behavior can be induced by the administration of cytokines itself or by cytokine-inducers such as lipopolysaccharide (LPS), the active fragment of endotoxin from Gram-negative bacteria. Preparations from roots of Pelargonium sidoides have been traditionally used in South African folk medicine for the treatment of different diseases (e.g. diarrhea, dysmenorrhea, hepatic disorders and respiratory tract infections including tuberculosis). Today, aqueous ethanolic extracts of Pelargonium sidoides are marketed mainly for respiratory tract infections. We studied the effects of the extract EPs 7630 and different fractions separated by ultrafiltration in an animal model of sickness behavior. The results of this study demonstrate that the extract EPs 7630 and the high-molecular weight fraction (F3) alleviate the symptoms of sickness behavior.

PMID:

17182237

 

 

Pediatrics. 2009 Aug;124(2):e172-9. Epub 2009 Jul 27.

Probiotic effects on cold and influenza-like symptom incidence and duration in children.

Leyer GJ, Li S, Mubasher ME, Reifer C, Ouwehand AC.

Source

Department of Research and Development, Danisco, Madison, Wisconsin, USA. greg.leyer@danisco.com

Abstract

OBJECTIVE:

Probiotic consumption effects on cold and influenza-like symptom incidence and duration were evaluated in healthy children during the winter season.

METHODS:

In this double-blind, placebo-controlled study, 326 eligible children (3-5 years of age) were assigned randomly to receive placebo (N = 104), Lactobacillus acidophilus NCFM (N = 110), or L acidophilus NCFM in combination with Bifidobacterium animalis subsp lactis Bi-07 (N = 112). Children were treated twice daily for 6 months.

RESULTS:

Relative to the placebo group, single and combination probiotics reduced fever incidence by 53.0% (P = .0085) and 72.7% (P = .0009), coughing incidence by 41.4% (P = .027) and 62.1% (P = .005), and rhinorrhea incidence by 28.2% (P = .68) and 58.8% (P = .03), respectively. Fever, coughing, and rhinorrhea duration was decreased significantly, relative to placebo, by 32% (single strain; P = .0023) and 48% (strain combination; P < .001). Antibiotic use incidence was reduced, relative to placebo, by 68.4% (single strain; P = .0002) and 84.2% (strain combination; P < .0001). Subjects receiving probiotic products had significant reductions in days absent from group child care, by 31.8% (single strain; P = .002) and 27.7% (strain combination; P < .001), compared with subjects receiving placebo treatment.

CONCLUSION:

Daily dietary probiotic supplementation for 6 months was a safe effective way to reduce fever, rhinorrhea, and cough incidence and duration and antibiotic prescription incidence, as well as the number of missed school days attributable to illness, for children 3 to 5 years of age.

PMID:

19651563

[PubMed - indexed for MEDLINE]

Free full text

 

J Am Geriatr Soc. 2004 Jan;52(1):20-4.

Can a short period of micronutrient supplementation in older institutionalized people improve response to influenza vaccine? A randomized, controlled trial.

Allsup SJ, Shenkin A, Gosney MA, Taylor S, Taylor W, Hammond M, Zambon MC.

Source

Departments of Geriatric Medicine, Clinical Chemistry, and Mathematical Sciences, University of Liverpool, Liverpool, United Kingdom. stephenallsup@tinyworld.co.uk

Abstract

OBJECTIVES:

To test the hypothesis that a micronutrient supplement can improve seroconversion after influenza immunization in older institutionalized people.

DESIGN:

: Randomized, double-blind, placebo-controlled study.

SETTING:

Nursing and residential homes in Liverpool, United Kingdom.

PARTICIPANTS:

One hundred sixty-four residents aged 60 and older from 31 homes were initially randomized; of these, 119 (72.6%) completed the study.

INTERVENTION:

Participants were randomized to receive a micronutrient supplement providing the reference nutrient intake for all vitamins and trace elements or identical placebo. Tablets were taken over an 8-week period during September and October 2000; influenza vaccine was administered 4 weeks after their commencement.

MEASUREMENTS:

The hemagglutination-inhibiting antibody response as defined by a fourfold or greater titer rise over 4 weeks and assessed separately for each of the three antigens contained in the 2000/2001 influenza vaccine (A/New Caledonia/20/99 (H1N1), A/Moscow/10/99 (H3N2), B/Beijing/184/93 (B)).

RESULTS:

Despite a significant increase in serum concentrations of vitamins A, C, D3, E, folate, and selenium in the supplemented group, there was no significant difference between groups (supplemented vs placebo, respectively) in the proportion of participants seroconverting to H1N1 (41% vs 49%, P=.374), H3N2 (49% vs 58%, P=.343), or B (41% vs 40%, P=.944).

CONCLUSION:

A micronutrient supplement providing the reference nutrient intake administered over 8 weeks had no beneficial effect on antibody response to influenza vaccine in older people living in long-term care.

PMID:

14687310