Evidence Based Complement Alternat Med.
2006 September; 3(3): 293–301.
Published online 2006 July 5.
doi: 10.1093/ecam/nel045.
PMCID: PMC1513149
Copyright © 2006 The Author(s)

Immunology and Homeopathy. 4. Clinical Studies—Part 1

Paolo Bellavite,1 Riccardo Ortolani,2 Francesco Pontarollo,1 Valeria
Piasere,1 Giovanni Benato,2 and Anita Conforti3
1Department of Scienze Morfologico-Biomediche, University of Verona,
Piazza L.A. Scuro, 37134 Verona, Italy
2Association for Integrative Medicine ‘Giovanni Scolaro’, University
of Verona, Piazza L.A. Scuro, 37134 Verona, Italy
3Department of Medicina e Sanità Pubblica, University of Verona,
Piazza L.A. Scuro, 37134 Verona, Italy
For reprints and all correspondence: Paolo Bellavite, University of
Verona, 37134 Verona, Italy. Tel: +39-045-8202978; Fax:
+39-045-8202978; E-mail: paolo.bellavite@univr.it
Received March 6, 2006; Accepted June 9, 2006.

This is an Open Access article distributed under the terms of the
Creative Commons Attribution Non-Commercial License (http://
creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted
non-commerical use, distribution, and reproduction in any medium,
provided the original work is properly cited.

This article has been corrected. See Evid Based Complement Alternat
Med. 2006 December; 3(4): 553.
This article has been cited by other articles in PMC.

Abstract
The evidence-based research of the effectiveness of homeopathic
medicines in common immunologic disorders is reviewed. In part 1, we
introduce methodological issues of clinical research in homeopathy,
and criteria utilized to evaluate the literature. Then 24 studies (12
randomized and 12 non-randomized) on common upper respiratory tract
infections and otorhinolaryngologic complaints are described. In part
2, the focus will be on allergic diseases and the effectiveness of
homeopathy will be globally evaluated and discussed using the criteria
of evidence-based medicine.
Keywords: evidence-based homeopathy, homeopathy, homeopatic
medications, immunology, otitis, sinusitis, stomatitis, upper
respiratory tract infections

Analyses
Infections of Upper Airways and Otorhinolaryngologic Diseases
References IntroductionHomeopathic research has developed over the
past 20 years with the increasingly greater use of modern medical
methods (clinical trials, observational studies, statistical
evaluations, computerized storage programs and instrumental or
laboratory testing). Over 200 clinical trials designed to verify the
efficacy of homeopathic treatments have been published, many (but not
all) of which have led to positive results. As in other medical
disciplines, statistically significant results could be reached by
pooling all of the methodologically reliable studies in a given area,
but with homeopathy this occurred very rarely, because few series have
been conducted for single conditions and because the experimental
approaches or the medicines used are too heterogeneous to be able to
conclude that any one protocol is efficacious. Some of these series
document clinically useful effects and differences against placebo (1–
5) and some series do not (6), or their evidence is ‘promising’ but
insufficient for drawing conclusions (7,8).

Recent controversies on the question of whether homeopathy is a
placebo response (9–13) have shown that an approved answer to this
dilemma is at present not possible, because evaluation of the evidence
and the inclusion or exclusion of papers from meta-analyses vary
according to pre-selected criteria, that differ in different reviews,
a sort of ‘bias’ of the observer (14,15). Moreover, there is a
noteworthy confusion concerning what type of ‘homeopathy’ is evaluated
(e.g. use of low or high potencies) and when homeopathy is accused for
its lack of ‘plausibility’ (9,16,17), the different modalities are not
suitably distinguished.

The aim of this lecture series is not to provide a meta-analysis of
homeopathic literature, neither to focus on the placebo question,
themes that have been addressed with variable results by others
(1,9,16,18–26), but to provide an overview of the best of available
homeopathic literature in the fields of immunoallergology and common
inflammatory diseases. As we have seen in the introductory lecture
(27), immunoallergology represents a bridge between homeopathy and
modern medicine insofar as it is a field in which it is easier to
apply concepts such as the effect of substances administered on the
basis of the logic of the ‘similar’ and the great sensitivity of
living systems to modulations induced by ultramicrodoses of natural or
endogenous substances. In this field, there is a body of pre-clinical
research suggesting that homeopathic remedies may regulate the immune
system at cellular and/or systemic levels (28–30). There are also
preliminary ex vivo observations of significant changes of immune
cells (CD4 lymphocytes) in people treated with high potencies of
homeopathic medicines (31) and, broadly speaking, it has been
suggested that T cells can be the target of immunoregulation by a
range of complementary and alternative medicines (32).

Patients with diseases of the immune system like allergies and asthma,
or with enhanced susceptibility to recurrent infections, or with
rheumatological diseases often have recourse to homeopathy as
‘alternative’ medicine (33,33–41). Unfortunately, there is paucity of
evidence-based recommendations using homeopathic remedies in these
conditions.

Evidence-based medicine will have increasing impact also in the field
of complementary and alternative medicine, but the systematic
evaluation of research evidence in homeopathy is an expectation that
requires suitable methods of evaluation (42,43). In this new and
controversial field, stringency of tools utilized to systematically
evaluate the scientific literature should always be accompanied by a
consensus concerning clinical protocols that significantly reflect
modalities of cure, types of follow-up and relevance of outcomes,
which can be different from those of conventional medicine. Otherwise
the results, instead of helping the judicious use of evidence in
making clinical decisions, become only the source of new controversy,
especially when disseminated by the media, as was in the recent
Lancet's meta-analysis that was inappropriately boosted by the
editorial title ‘The end of homeopathy’(44).

Here, we have distinguished publications in two major groups, each of
which holds a rationale for deployment of homeopathic remedies. A
first group (described in this part of the review) includes
pathologies consisting of anomalous susceptibility to infections that
may be, at least in part, due to inadequacy of efficiency of the
immune system in the rejection of an extraneous aggressor. The second
group (described in a subsequent part of the review), includes
pathologies due to hypersensitivity of the immune system, the most
widespread of which is immediate hypersensitivity, or allergy, and its
major manifestations at the level of respiratory system. For each
group of pathologies, the different homeopathic methods utilized,
namely (i) classical individualized homeopathy, (ii) isotherapy, (iii)
specific medicines for each disease or symptom (pluralist or clinical
approach) or (iv) complex formulations (used particularly in
homotoxicology) are dealt with in separately. A general discussion of
the evidence-based homeopathy in these fields will be reported in the
second part of the review.

Infections of Upper Airways and Otorhinolaryngologic Diseases
References AnalysesThis review reports literature on human subjects
available to us from 1978 to 2006. Principal information sources were
current reading of major CAM journals during the past 15 years,
screening of the monthly publication of complementary medicine index
(British Library), of the databases of Central Council for research in
Homeopathy and of Hom-inform Information Service, literature searching
using Medline, CAM on PubMed, Cochrane Database of Systematic Reviews
and CAMbase, cross-referencing. We have also checked the existing
systematic reviews and meta-analyses that cover trials of
immunoallergology. The analysis includes controlled clinical trials
(with and without randomization), observational studies and case
series. All forms of homeopathic intervention are included. That a few
published papers, still unknown to us, escaped from our screening, is
conceivable; in any case, we have not made any pre-selection, based
for example on the quality of studies or on their outcomes (positive
versus negative) so that the present review is certainly
representative of the ‘state of the art’ of international literature
in the considered fields.

When complementary and complex interventions such as acupuncture or
homeopathy are considered, there is no consensus on the quality
criteria used to classify the clinical data according to the
importance of treatment outcomes, the scientific strength and the
reliability (11,45,46). Problems arise especially concerning blinding
and concealment, follow-up indexes particularly in chronic cases,
healing markers, primary and secondary outcomes, and the validity of
experimental versus observational studies. Therefore, to allow a semi-
quantitative ranking of homeopathic treatment studies, we have adopted
the following two criteria.

First, we have classified the publications according to the type of
study, using, with slight modifications, the classification system
that has been developed by the National Cancer Institute for human
studies of complementary and alternative medicine in cancer studies
(http://www.cancer.gov/cancertopics/pdq/levels-evidence-cam/
HealthProfessional/page2). According to this classification, the score
in descending order of strength is reported in Table 1. The main
modification with respect to the NCI classification is that we have
included the randomized (non-blinded) equivalence studies, comparing
two modalities of therapy, in level 1b and the non-randomized
equivalence studies in level 2. Those types of studies have increasing
importance in CAM literature (47).

Table 1
Classification of clinical studies in homeopathy

A second criterion that may help in ‘weighing’ each paper is the
publication type, which we scored according to a classification where
the top papers are those published in mainstream medical literature
and the last level is provided by publications in books or conference
proceedings (Table 2). Communications reporting single cases or expert
opinions were excluded. Although this order may be questionable for a
number of reasons (especially as concerns the difference between
mainstream and complementary/alternative medicine journals), we
believe that it may facilitate the reader in judging the grade of
evidence provided by each study.

Table 2
Classification of publications in homeopathy according to the type

Infections of Upper Airways and Otorhinolaryngologic Diseases
References Infections of Upper Airways and Otorhinolaryngologic
DiseasesHomeopathic research in otorhinolaryngology includes studies
of acute and chronic rhinitis, otitis media, sinusitis and
tonsillitis. Here, the diseases of infectious origin are considered,
while the allergic diseases are considered later. Several homeopathic
researchers have worked on these diseases, which are frequent in the
general population, with often positive results. The unnecessary use
of antibiotics in the initial treatment of acute otitis media and URI
is currently being questioned. Homeopathy has been used historically
to treat this illness, and it is interesting to determine if there are
methodologically rigorous trials to support its effectiveness.

We also report a relevant study on post-chemotherapy stomatitis, which
is caused both by direct mucosal damage and by infections due to
immunodeficiency. We have omitted the trials on influenza both because
of limited space and existence of recent systematic reviews covering
the topic (26,48). A summary in chronological order is reported in
Table 3 and a brief outline of each protocol with the main results of
different homeopathic strategies is given as follows.

Table 3
Homeopathic clinical studies on infections of upper airways and ear–
nose–throat diseases

Classical Individualized Homeopathy
The first report of classical homeopathy is relatively recent, dating
in 1997 when Friese et al. (59) reported an open study comparing the
results obtained treating otitis media in children, treated using two
different medical approaches. They compared classical unitary
homeopathic remedies (Aconitum, Apis mel., Belladonna, Lachesis,
Pulsatilla, Silicea, Lycopodium, Chamomilla and Capsicum) prescribed
after an individual homeopathic case analysis, with conventional
therapy based on antibiotics, mucolytics and antipyretics. The
duration of pain was 2 days in the homeopathic group and 3 days in the
conventional therapy group and the duration of therapy was 4 and 10
days, respectively. The latter difference was statistically
significant, but it should be noted that the duration of antibiotic
therapy for these conditions cannot be shorter than a week, so this
comparison may not reflect the clinical outcomes. In brief, this
pragmatic study comparing homeopathic with conventional therapy showed
that results were similar, but with a trend in favor of homeopathy.
In an open, prospective, multicenter study, Kruse (60) evaluated a
group of children with otitis media for 6 weeks, controlling results
against conventional therapy. The homeopathy group was treated with
single remedies like Aconitum 30×, Apis 6×, Belladonna 30×, Capsicum
6×, Chamomilla 3×, Lachesis 12× and other remedies; the reference
group was treated with antibiotics, secretolytics, antipyretics and
sympathomimetics such as nasal sprays. In the two groups the number of
children remaining relapse-free and the average duration of pain were
similar.

A Negative Trial and Subsequent Arguments
De Lange de Klerk (62) performed a double-blind, randomized study that
evaluated the frequency, duration and severity of rhinitis,
pharyngitis and tonsillitis in a group of children. The homeopathic
prescription included ‘constitutional’ remedies for preventive
purposes and remedies treating acute phases. The year-long therapy was
continuously adjusted on an individual basis, and data were collected
by means of diaries kept by parents and attending physicians. Results
showed that homeopathic therapy was slightly but not significantly
better than placebo. The paper was criticized by homeopathic expert
clinicians (73) and methodologists (15) maintaining that homeopathy in
that study required beneficial proof in addition to conventional
therapy. If homeopathy was effective, control children would require
more antibiotics and tonsillectomy, and this was the case; such
surplus of conventional therapies could have created false negative
results.

Observations of Benefit
The purpose of the observational study of Frei and Thurneysen (64) was
to determine how many children with acute otitis media are relieved of
pain with individualized homeopathic treatment. Children with this
condition received a first individualized homeopathic medicine in the
pediatric office. If pain reduction was not sufficient after 6 h, a
second (different) homeopathic medicine was given. After a further 6
h, children who had not reached pain control were started on
antibiotics. Pain control was achieved in 39% of the patients after 6
h, another 33% after 12 h. Compared with literature's data, the
authors stated that the resolution rate is 2.4 times faster than in
untreated cases. The six more frequently prescribed remedies were
Pulsatilla, Belladonna, sulphur, phosphorus, calcium carbonicum,
Lycopodium.
An interesting multicenter, prospective, observational study in a real
world medical setting compared the effectiveness of homeopathy with
conventional medicine (65). Thirty investigators with conventional
medical licenses at six clinical sites in four countries enrolled a
series of patients with at least one of the following three
complaints: upper respiratory tract complaints including allergies;
lower respiratory tract complaints including allergies; or ear
complaints. Four hundred and fifty-six patient visits were compared.
In any case, homeopathy appeared to be at least as effective as
conventional medical care in the treatment of patients with these
three conditions.

A randomized double-blind placebo control pilot study was conducted
(66) in children with otitis media. Subjects having middle ear
effusion and ear pain and/or fever for no more than 36 h entered into
the study. They received either an individualized homeopathic medicine
or a placebo administered orally three times daily for 5 days, or
until symptoms subsided. There were fewer treatment failures in the
group receiving homeopathy, but these differences were not
statistically significant. Diary scores showed a significant decrease
in symptoms after treatment in favor of homeopathy (P < 0.05).

Controversial Findings
An equivalence trial was performed by Steinsbekk et al. (70), who
investigated whether individualized treatment by homeopaths is
effective in preventing childhood upper respiratory tract infections
(URTI). Children recruited from a group previously diagnosed with
URTI, were randomly assigned to receive either homeopathic care or to
conventional health care. There was a significant difference in median
total symptom score in favor of homeopathic care compared to the
control group. On the other hand, negative results were obtained by
the same group (71) in a double-blind placebo-controlled randomized
trial. Children with recurrent URTI were randomly assigned to receive
either placebo or homeopathic medicines in 30c potency, chosen by
parents using a simplified constitutional indications for the three
medicines most frequently prescribed by Norwegian homeopaths for this
group of patients (74). When necessary, patients of both groups were
allowed to take conventional medication. There was no difference in
the predefined primary outcome between the two groups. This can be due
to the lack of effect of the highly diluted homeopathic medicines, to
the interference of conventional treatment, or the process of
selection of medicines, that was performed by parents.

Cost-Effectiveness
A study to compare effectiveness and costs of two treatment strategies
(‘homeopathic strategy’ versus ‘antibiotic strategy’) used in routine
medical practice by allopathic and homeopathic GPs in the treatment of
recurrent acute rhinopharyngitis in children was recently published
(72). Data from a large series of patients were analyzed and grouped
according to type of drug prescribed, episodes of acute
rhinopharyngitis, complications, adverse effects and medical costs.
The results showed that the ‘homeopathic strategy’ yielded
significantly better results than the ‘antibiotic strategy’ in terms
of number of episodes of rhinopharyngitis, number of complications and
quality of life with lower direct medical costs in favor of
homeopathy. Of course, these findings should be confirmed with
randomized studies on homogeneous groups of patients.

Fixed Prescription of Low-Potencies
Although people are best treated with an individualized homeopathic
remedy chosen by a professional homeopath (75), several trials have
found that some common homeopathic remedies or their combinations may
be at least as effective as conventional medications.
An early study on the effect of a low-dilution homeopathic medicine on
the common cold was done by Gassinger (49). The authors compared the
effect of Eupatorium perfoliatum 2× with that of acetylsalicylic acid.
Neither the subjective symptoms, nor body temperature, nor laboratory
data showed any significant differences in the two groups, which led
the authors to conclude that the homeopathic treatment was as
effective as the allopathic treatment. Of course, this is not a direct
evidence of the efficacy of homeopathy, mostly because even the
effectiveness of analgesic/antipyretic medications in the common cold
is uncertain (76).

Wiesenauer et al. (54) compared the effects of three different
homeopathic treatments and placebo in patients with acute and chronic
sinusitis. In this randomized, double-blind study the patients were
divided into four groups: group A: Luffa operculata 4× + Kalium
bichromicum 4× + Cinnabaris 3×; group B: K. bichromicum 4× +
Cinnabaris 3×; group C: Cinnabaris 3×; and group D: placebo. The study
did not reveal any difference in therapeutic effects in the four
groups. Their conclusion was that, unless other data emerge from a
study of individual homeopathic prescriptions (‘repertorization’), the
drugs should not be considered active in acute or chronic sinusitis in
the general population; they also pointed out that similar negative
results have been obtained with antibiotics, nasal decongestants and
drainage of the nasal cavities.

Complex Formulations
To cure one or few symptoms, particularly in short-lasting and acute
conditions, complex formulations or mixtures of homeopathic remedies
are often used. The complex homeopathy was born a little after the
original discovery of Hahnemann and it is not fully comparable with
homotoxicology which is a specific methodological way to prescribe
complex homeopathic drugs. The latter procedure, also called
‘Biological medicine’, was developed in the second half of twentieth
century (77,78), starting from Germany. Although homotoxicology is
characterized by methods of diagnosis and prescription very different
from Hahnemann's original homeopathy, most of the formulations have
their roots in the materia medica of single components and have the
recognition of ‘homeopathic medicines’ by EU drug legislation.
Trials assessing the effectiveness of complex medicines in relieving
specific symptoms are easier to be conducted as compared with those
that require individualized treatment and continuous adjustment of
therapy. Moreover, there is much higher commercial interest to such
formulations than to single remedies, which cannot be patented. These
reasons explain why there are relatively more studies of complex
formulations than of single homeopathic remedies.

The primary objective of treating of inflammatory diseases of upper
respiratory tract (rhinitis, uncomplicated sinusitis) is to relieve
obstruction and to improve associated symptoms. In this respect, a
homeopathic remedy may be seen much like a local decongestant helping
restoration of unrestricted respiration and drainage of nasal sinuses,
factors that reduce the risk of further complications and of
chronicity. However, many homeopathic formulations contain remedies
that are expected to act as immunostimulators and/or according to
isopathic principles of cure.

A homeopathic remedy, L52, a complex formulation containing E.
perfoliatum 3×, Aconitum napellus 4×, Bryonia alba 3×, Arnica montana
4×, Gelsemium sempervirens 6×, Cinchona 4×, Belladonna 4×, Drosera 3×,
Senega 3× showed promising results, in a double-blind study against
placebo, for relief of symptoms of URTI (50), but not in prevention of
flu in a large double-blind, placebo-controlled study (~1200
participants) (79).

In a single-blind randomized trial, army soldiers suffering from
common cold were treated with aspirin or with a complex homeopathic
preparation called Grippheel (Aconitum 4×, Bryonia 4×, Lachesis 12×,
E. perfoliatum 3×, phosphorus 5×) (52). Comparison between the changes
in clinical status and in subjective disorders on days 4 and 10 and
between the duration of the periods off work in two groups revealed no
significant differences, leading to the conclusion that the two drugs
are equieffective. More recently, the same medicine has been evaluated
in a prospective, observational cohort study in patients affected by
mild viral infections of upper respiratory tract (68) with encouraging
results, consisting of an equivalent effectiveness of homeopathy and
conventional medications.

In the field of respiratory diseases, mention must be made of a study
by some French researchers (51) who treated dry cough with a syrup
based on the plant Drosera and another nine substances in 3c dilution,
and found that it was much better than placebo: after 1 week of
therapy, the symptom had become less severe or had disappeared in 20
out of 30 treated patients, as against only 8 out of 30 in placebo
group.

Euphorbium
Sprenger (53) conducted an open study of a low-dilution complex
homeopathic preparation, Euphorbium compositum, used as a nasal spray
in patients with acute or chronic rhinitis. The product consisted of
Euphorbium resinifera 4×, Pulsatilla pratensis 2×, L. operculata 2×,
Mercurius iodatus ruber 6×, Mucosa nasalis suis 6×, Hepar sulphuris
calcareum 10×, Argentum nitricum 10× and Sinusitis nosode 13×, and was
administered at a dose of 1–2 puffs per nostril 3–5 times a day. The
physician's judgment of the therapy was good in 83% of cases, whereas
tolerability was excellent in 55.4% of cases and good in 44.6%.
Another observational, uncontrolled study on patients suffering from
chronic rhinopathy associated with a previous long-term application of
medication (abuse of nasal spray) showed positive results in 22 out of
26 patients, with normalization of rhinomanometric tests (56).
Subsequently, Weiser and Clasen (57) studied the clinical
effectiveness of the same complex E. compositum in a double-blind,
randomized, placebo-controlled study in subjects with chronic
sinusitis. The treated group showed a significant improvement in terms
of subjective symptoms such as respiratory obstruction, sensation of
internal pressure and pain, but there was no substantial variation in
instrumental tests. An overall evaluation showed a better improvement
in verum group as in placebo group.

A further open, multicenter, prospective, active-controlled cohort
study was carried out more recently on the homeopathic complex E.
compositum (nasal drops), whose effectiveness and tolerability was
compared with the reference allopathic drug xylometazoline (69).
Clinically relevant reductions in intensities of disease-specific
symptoms were observed with both groups. Non-inferiority of the
homeopathic complex remedy to xylometazoline could be shown for all
studied variables. Tolerability was good for both therapies.
Interestingly, it has been reported that some components of this
medicine, e.g. Euphorbium and Pulsatilla, but not Luffa, as plant
extract (not homeopathic preparations), have a direct antiviral
(respiratory syncytial virus and herpes simplex virus type 1) effect
in vitro (80).

Other Low-Dilution Complexes
Zenner and Metelmann (55) published the results of an open study of a
complex preparation, Lymphomyosot drops (Myosotis arvensis 3×,
Veronica officinalis 3×, Teucrium scorodonia 3×, Pinus sylvestris 4×,
and even other 13 plant or mineral components) in treatment of
pharyngitis and tonsillitis. In a group of patients with tonsillitis,
most of them recorded ‘excellent, good or satisfactory’ improvements
after treatments lasting between 1 and 6 months.
A different complex that has been used in this kind of respiratory
complaints is Engystol-N (made of Vincetoxicum 6×, 10× and 30×, sulfur
4× and 10×). A randomized, double-blind, placebo-controlled trial
assessed the efficacy of this formulation, administered twice weekly
as intravenous injection, for prophylaxis of common cold and flu (58).
The frequency of occurrence of flu or common cold was not changed by
treatments, but the average length of illness and the severity of
symptoms were less for the verum group than for the placebo group. No
statistical analysis of data was provided.

The efficacy of three plants used in homeopathy to treat acute
tonsillitis was evaluated with an open trial (61). A fixed combination
of low dilutions of three plant substances (Phytolacca americana,
Guajacum officinale and Capsicum annuum) was used in patients with
this condition and no antibiotics were used. According to materia
medica, this homeopathic complex remedy should be characterized by
immunomodulatory, analgesic and anti-inflammatory properties. A
decrease in objective and subjective symptoms of acute tonsillitis
symptoms was observed after treatment startup; no serious adverse
effects were reported.

The efficacy and safety of a fixed combination homeopathic medication
(Sinusitis PMD) consisting of Lobaria pulmonaria, L. operculata and
potassium dichromate were investigated in an open-label practice-based
study of patients with acute sinusitis (63). Most patients received
only test medication and no antibiotics. After 4 days of treatment,
secretolysis had increased significantly and typical sinusitis
symptoms, such as headache, pressure pain at nerve exit points and
irritating cough, were reduced. The average treatment duration was 2
weeks. At the end of treatment, most patients described themselves as
symptom-free or significantly improved. Adverse drug effects were not
reported.

A Remedy for Stomatitis
An Israeli team (67) assessed a complex homeopathic preparation
(Traumeel-S, containing 4×–12× potencies of A. montana and other plant
extracts and minerals) for its effect in chemotherapy-associated
stomatitis, a common consequence of chemotherapy and a condition for
which there is little effective treatment. The study was conducted in
children and young adults who had undergone stem cell transplantation,
in a randomized, placebo-controlled, double-blind clinical trial. The
medicine was administered as a mouth rinse, five times daily. Thirty-
three percent of patients in active treatment group did not develop
stomatitis, compared with only 7% in placebo group. Stomatitis
worsened in 47% of patients in active treatment group compared with
93% in placebo group. The stomatitis scores were better in verum group
(P < 0.01). It is worth noting that, at variance with respect to most
homeopathic medicines, the efficacy and the action mechanisms of
Traumeel were repeatedly characterized also in pre-clinical studies,
as described in previous reviews of this series (28,29).

Infections of Upper Airways and Otorhinolaryngologic Diseases

References
1.Linde K, Clausius N, Ramirez G, Melchart D, Eitel F, Hedges LV, et
al. Are the clinical effects of homeopathy placebo effects? A meta-
analysis of placebo-controlled trials. Lancet. 1997;350:834–43.
[PubMed]
2.Ludtke R, Wiesenauer M. A meta-analysis of homeopathic treatment of
pollinosis with Galphimia glauca. Wien Med Wochenschr. 1997;147:323–7.
[PubMed]
3.Wiesenauer M, Ludtke R. A metaanalysis of the homeopahic treatment
of pollinosis with Galphimia glauca. Forsch Komplementarmed.
1996;3:230–4.
4.Taylor MA, Reilly D, Llewellyn-Jones RH, McSharry C, Aitchison TC.
Randomised controlled trial of homoeopathy versus placebo in perennial
allergic rhinitis with overview of four trial series. Br Med J.
2000;321:471–6. [PubMed]
5.Tveiten D, Bruset S. Effect of Arnica D30 in marathon runners.
Pooled results from two double-blind placebo controlled studies.
Homeopathy. 2003;92:187–9. [PubMed]
6.McCarney RW, Lasserson TJ, Linde K, Brinkhaus B. An overview of two
cochrane systematic reviews of complementary treatments for chronic
asthma: acupuncture and homeopathy. Respir Med. 2004;98:687–96.
[PubMed]
7.Cucherat M, Haugh MC, Gooch M, Boissel JP. Evidence of clinical
efficacy of homeopathy. A meta-analysis of clinical trials. HMRAG.
Homeopathic Medicines Research Advisory Group. Eur J Clin Pharmacol.
2000;56:27–33. [PubMed]
8.Long L, Ernst E. Homeopathic remedies for the treatment of
osteoarthritis: a systematic review. Br Homeopath J. 2001;90:37–43.
[PubMed]
9.Shang A, Huwiler-Müntener K, Nartey L, Jüni P, Dörig S, Sterne JAC,
et al. Are the clinical effects of homoeopathy placebo effects?
Comparative study of placebo-controlled trials of homoeopathy and
allopathy. Lancet. 2005;366:726–32. [PubMed]
10.Kiene H, Kienle GS, Schon-Angerer T. Failure to exclude false
negative bias: a fundamental flaw in the trial of Shang et al. J
Altern Complement Med. 2005;11:783. [PubMed]
11.Bellavite P, Pitari G, Italiano M. Homeopathy and placebo.
Homeopathy. 2006;95:51. [PubMed]
12.Linde K, Jonas W. Are the clinical effects of homoeopathy placebo
effects? Lancet. 2005;366:2081–2. [PubMed]
13.Walach H, Jonas W, Lewith G. Are the clinical effects of
homoeopathy placebo effects? Lancet. 2005;366:2081–6. [PubMed]
14.Frass M, Schuster E, Muchitsch I, Duncan J, Gei W, Kozel G, et al.
Bias in the trial and reporting of trials of homeopathy: a fundamental
breakdown in peer review and standards? J Altern Complement Med.
2005;11:780–2. [PubMed]
15.Kiene H, Kienle GS, Schon-Angerer T. Bias in meta-analysis.
Homeopathy. 2006;95:54. [PubMed]
16.Kleijnen J, Knipschild P, ter Riet G. Clinical trials of
homoeopathy. Br Med J. 1991;302:316–23. [PubMed]
17.Ernst E. Is homeopathy a clinically valuable approach? Trends
Pharmacol Sci. 2005;26:547–8. [PubMed]
18.Reilly DT, Taylor MA, Beattie NG, Campbell JH, McSharry C,
Aitchison TC, et al. Is evidence for homoeopathy reproducible? Lancet.
1994;344:1601–6. [PubMed]
19.Coletti M. Homéopathie. A' la recherche de la demonstration d'une
activité clinique spècifique (suite). La Revue Prescrire. 1999;19:212–
7.
20.Linde K, Scholz M, Ramirez G, Clausius N, Melchart D, Jonas WB.
Impact of study quality on outcome in placebo-controlled trials of
homeopathy. J Clin Epidemiol. 1999;52:631–6. [PubMed]
21.Ernst E, Pittler MH. Re-analysis of previous meta-analysis of
clinical trials of homeopathy. J Clin Epidemiol. 2000;53:1188.
[PubMed]
22.Linde K, Hondras M, Vickers A, ter Riet G, Melchart D. Systematic
reviews of complementary therapies—an annotated bibliography. Part 3:
homeopathy. BMC Complement Altern Med. 2001;1:4. [PubMed]
23.Jonas WB, Anderson RL, Crawford CC, Lyons JS. A systematic review
of the quality of homeopathic clinical trials. BMC Complement Altern
Med. 2001;1:12. [PubMed]
24.Jonas WB, Kaptchuk TJ, Linde K. A critical overview of homeopathy.
Ann Intern Med. 2003;138:393–9. [PubMed]
25.Linde K, ter Riet G, Hondras M, Melchart D, Willich SN.
Characteristics and quality of systematic reviews of acupuncture,
herbal medicines, and homeopathy. Forsch Komplementarmed Klass
Naturheilkd. 2003;10:88–94. [PubMed]
26.Mathie RT. The research evidence base for homeopathy: a fresh
assessment of the literature. Homeopathy. 2003;92:84–91. [PubMed]
27.Bellavite P, Conforti A, Piasere V, Ortolani R. Immunology and
homeopathy. 1. Historical background. Evid Based Complement Alternat
Med. 2005;2:441–52. [PubMed]
28.Bellavite P, Conforti A, Pontarollo F, Ortolani R. Immunology and
homeopathy. 2. Cells of the immune system and inflammation. Evid Based
Complement Alternat Med. 2006;3:13–24. [PubMed]
29.Bellavite P, Conforti A, Ortolani R. Immunology and homeopathy. 3.
Experimental studies on animal models. Evid Based Complement Alternat
Med. 2006;3:171–86. [PubMed]
30.Belon P, Banerjee P, Choudhury S, Banerjee A, Biswas SJ, Karmakar
S, et al. Can administration of potentized homeopathic remedy,
arsenicum album, alter antinuclear antibody (ANA) titer in people
living in high-risk arsenic contaminated areas? I. A correlation with
certain hematological parameters. Evid Based Complement Alternat Med.
2006;3:99–107. [PubMed]
31.Kuzeff RM. Homeopathy, sensation of well-being and CD4 levels: a
placebo-controlled, randomized trial. Complement Ther Med. 1998;6:4–9.
32.Vojdani A, Erde J. Regulatory T cells, a potent immunoregulatory
target for CAM researchers: the ultimate antagonist (I). Evid Based
Complement Alternat Med. 2006;3:25–30. [PubMed]
33.Blanc PD, Trupin L, Earnest G, Katz PP, Yelin EH, Eisner MD.
Alternative therapies among adults with a reported diagnosis of asthma
or rhinosinusitis: data from a population-based survey. Chest.
2001;120:1461–7. [PubMed]
34.Schafer T, Riehle A, Wichmann HE, Ring J. Alternative medicine in
allergy. Allergy. 2002;57:694–700. [PubMed]
35.Chandrashekara S, Anilkumar T, Jamuna S. Complementary and
alternative drug therapy in arthritis. J Assoc Physicians India.
2002;50:225–7. [PubMed]
36.Schafer T. Epidemiology of complementary alternative medicine for
asthma and allergy in Europe and Germany. Ann Allergy Asthma Immunol.
2004;93:S5–10. [PubMed]
37.Bielory L, Russin J, Zuckerman GB. Clinical efficacy, mechanisms of
action, and adverse effects of complementary and alternative medicine
therapies for asthma. Allergy Asthma Proc. 2004;25:283–91. [PubMed]
38.Becker-Witt C, Ludtke R, Weisshuhn TE, Willich SN. Diagnoses and
treatment in homeopathic medical practice. Forsch Komplementarmed
Klass Naturheilkd. 2004;11:98–103. [PubMed]
39.Sevar R. Audit of outcome in 455 consecutive patients treated with
homeopathic medicines. Homeopathy. 2005;94:215–21. [PubMed]
40.Breuer GS, Orbach H, Elkayam O, Berkun Y, Paran D, Mates M, et al.
Perceived efficacy among patients of various methods of complementary
alternative medicine for rheumatologic diseases. Clin Exp Rheumatol.
2005;23:693–6. [PubMed]
41.Passalacqua G, Compalati E, Schiappoli M, Senna G. Complementary
and alternative medicine for the treatment and diagnosis of asthma and
allergic diseases. Monaldi Arch Chest Dis. 2005;63:47–54. [PubMed]
42.Chiappelli F, Prolo P, Cajulis OS. Evidence-based research in
complementary and alternative medicine I: history. Evid Based
Complement Alternat Med. 2005;2:453–8. [PubMed]
43.Chiappelli F, Prolo P, Rosenblum M, Edgerton M, Cajulis OS.
Evidence-based research in complementary and alternative medicine II:
the process of evidence-based research. Evid Based Complement Alternat
Med. 2006;3:3–12. [PubMed]
44.Editorial. The end of homeopathy. Lancet. 2005;366:690.
45.Paterson C, Dieppe P. Characteristic and incidental (placebo)
effects in complex interventions such as acupuncture. Br Med J.
2005;330:1202–5. [PubMed]
46.Weatherley-Jones E, Thompson EA, Thomas KJ. The placebo-controlled
trial as a test of complementary and alternative medicine:
observations from research experience of individualised homeopathic
treatment. Homeopathy. 2004;93:186–9. [PubMed]
47.Ernst E. Equivalence and non-inferiority trials of CAM. Evid Based
Complement Alternat Med. 2004;1:9–10. [PubMed]
48.Vickers AJ, Smith C. Homoeopathic Oscillococcinum for preventing
and treating influenza and influenza-like syndromes. Cochrane Database
Syst Rev. 2004 ; CD001957.
49.Gassinger CA, Wunstel G, Netter P. A controlled clinical trial for
testing the efficacy of the homeopathic drug Eupatorium perfoliatum D2
in the treatment of common cold. Arzneimittelforschung. 1981;31:732–6.
[PubMed]
50.Lecoq PL. L-52. Les voies thérapeuthiques des syndromes grippaux.
Cah Biothér. 1985;87:65–73.
51.Bordes LR, Dorfman P. Evaluation de l'activité antitussive du sirop
Drosetux: Etude en double aveugle versus placebo. Cahiers
d'Otorhinolaryngologie. 1986;21:731–4.
52.Maiwald VL, Weinfurtner T, Mau J, Connert WD. Therapy of common
cold with a homeopathic combination preparation in comparison with
acetylsalicylic acid. A controlled, randomized double-blind study.
Arzneimittelforschung. 1988;38:578–82. [PubMed]
53.Sprenger F. The therapy of rhinitis. Biol Ther. 1989;7:60–3.
54.Wiesenauer M, Gaus W, Bohnacker U, Haussler S. Efficiency of
homeopathic preparation combinations in sinusitis. Results of a
randomized double blind study with general practitioners.
Arzneimittelforschung. 1989;39:620–5. [PubMed]
55.Zenner S, Metelmann H. Therapeutic use of lymphomyosot, result of a
multicentric use observation study on 3512 patients. Biol Ther.
1990;8:49–69.
56.Connert WD, Maiwald J. The therapy of rhinopathy as associated with
previous abuse of nasal spray and with vasomotor influences. Biol
Ther. 1991;9:182–6.
57.Weiser M, Clasen BP. Controlled double-blind study of a
homoeopathic sinusitis medication. Biol Ther. 1994;13:4–11.
58.Heilmann A. A combination injection preparation as a prophylactic
for flu common colds. Biol Ther. 1994;13:249–53.
59.Friese KH, Kruse S, Ludtke R, Moeller H. The homoeopathic treatment
of otitis media in children—comparisons with conventional therapy. Int
J Clin Pharmacol Ther. 1997;35:296–301. [PubMed]
60.Kruse, S. Otitis media bei kindern. Stuttgart: Hippokrates Verlag;
1998. Edition Forschung.
61.Wiesenauer M. Comparison of solid and liquid forms of homeopathic
remedies for tonsillitis. Adv Ther. 1998;15:362–371. [PubMed]
62.de Lange de Klerk ES. A homeopathic nosode for influenza-like
syndromes. Forsch Komplementarmed. 1999;6:31–2. [PubMed]
63.Adler M. Efficacy and safety of a fixed-combination homeopathic
therapy for sinusitis. Adv Ther. 1999;16:103–11. [PubMed]
64.Frei H, Thurneysen A. Homeopathy in acute otitis media in children:
treatment effect or spontaneous resolution? Br Homeopath J.
2001;90:180–2. [PubMed]
65.Riley D, Fischer M, Singh B, Haidvogl M, Heger M. Homeopathy and
conventional medicine: an outcomes study comparing effectiveness in a
primary care setting. J Altern Complement Med. 2001;7:149–59. [PubMed]
66.Jacobs J, Springer DA, Crothers D. Homeopathic treatment of acute
otitis media in children: a preliminary randomized placebo-controlled
trial. Pediatr Infect Dis J. 2001;20:177–83. [PubMed]
67.Oberbaum M, Yaniv I, Ben Gal Y, Stein J, Ben Zvi N, Freedman LS, et
al. A randomized, controlled clinical trial of the homeopathic
medication Traumeel S in the treatment of chemotherapy-induced
stomatitis in children undergoing stem cell transplantation. Cancer.
2001;92:684–90. [PubMed]
68.Rabe A, Weiser M, Klein P. Effectiveness and tolerability of a
homoeopathic remedy compared with conventional therapy for mild viral
infections. Int J Clin Pract. 2004;58:827–32. [PubMed]
69.Ammerschlager H, Klein P, Weiser M, Oberbaum M. Treatment of
inflammatory diseases of the upper respiratory tract—comparison of a
homeopathic complex remedy with xylometazoline. Forsch Komplementarmed
Klass Naturheilkd. 2005;12:24–31. [PubMed]
70.Steinsbekk A, Fonnebo V, Lewith G, Bentzen N. Homeopathic care for
the prevention of upper respiratory tract infections in children: a
pragmatic, randomised, controlled trial comparing individualised
homeopathic care and waiting-list controls. Complement Ther Med.
2005;13:231–8. [PubMed]
71.Steinsbekk A, Bentzen N, Fonnebo V, Lewith G. Self treatment with
one of three self selected, ultramolecular homeopathic medicines for
the prevention of upper respiratory tract infections in children. A
double-blind randomized placebo controlled trial. Br J Clin Pharmacol.
2005;59:447–55. [PubMed]
72.Trichard M, Chaufferin G, Nicoloyannis N. Pharmacoeconomic
comparison between homeopathic and antibiotic treatment strategies in
recurrent acute rhinopharyngitis in children. Homeopathy. 2005;94:3–9.
[PubMed]
73.Fisher P, Reilly DT, Spence D, Ratsey D, Rose B, English J.
Homoeopathy for recurrent upper respiratory tract infections. No
children received no treatment. Br Med J. 1995;310:256. [PubMed]
74.Steinsbekk A, Bentzen N, Fonnebo V, Lewith G. The use of simplified
constitutional indications for self-prescription of homeopathic
medicine. Complement Ther Med. 2004;12:112–7. [PubMed]
75.Swayne J. Richard Hughes Memorial Lecture 2004. Homeopathy,
wholeness and healing. Homeopathy. 2005;94:37–43. [PubMed]
76.Graham NM, Burrell CJ, Douglas RM, Debelle P, Davies L. Adverse
effects of aspirin, acetaminophen, and ibuprofen on immune function,
viral shedding, and clinical status in rhinovirus-infected volunteers.
J Infect Dis. 1990;162:1277–82. [PubMed]
77.Reckeweg, HH. Homotoxikologie. Ganzheitsschau Einer Synthese der
Medizin. Baden-Baden: Aurelia Verlag; 1981.
78.Schmid, F.;Rimpler, M.; Wemmer, U. Antihomotoxische Medizin. Bd.1.
Baden-Baden: Aurelia; 1996.
79.Ferley JP, Putignat N, Azzopardi Y, Charrel M, Zmirou D. Evaluation
en médecine ambulatoire de l'activité d'un complexe homéopathique dans
la prévention de la grippe et des syndromes grippaux. Immunol Med.
1987;20:22–8.
80.Glatthaar-Saalmuller B, Fallier-Becker P. Antiviral action of
Euphorbium compositum and its components. Forsch Komplementarmed Klass
Naturheilkd. 2001;8:207–12. [PubMed]

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