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Homeopathic Treatments of Upper Respiratory and Otorhinolaryngologic Infections: A Review of Randomized and Observational Studies

  • Homeopathic Medicine School of Verona
*Corresponding author: Paolo Bellavite, Department of Medicine, Section of
General Pathology, University of Verona, Strada Le Grazie 8, 37134, Verona, Ita-
ly, Tel: +39 0458027120; Fax: +39 0458027127; E-mail:
Citation: Bellavite P, Marzotto M, Andreoli B (2019) Homeopathic Treatments
of Upper Respiratory and Otorhinolaryngologic Infections: A Review of Ran-
domized and Observational Studies. J Altern Complement Integr Med 5: 068.
Received: May 28, 2019; Accepted: June 06, 2019; Published: June 13, 2019
Copyright: © 2019 Bellavite P, et al. This is an open-access article distributed
under the terms of the Creative Commons Attribution License, which permits un-
restricted use, distribution, and reproduction in any medium, provided the original
author and source are credited.
Homeopathic medicines are often used in the hope of resolving
ailments not successfully cured by conventional drugs, or as a com-
plementary treatment to reduce the consumption of anti-inammato-
ry drugs or steroids that may have adverse effects, to relieve certain
symptoms and improve the quality of life [1-8]. A worldwide median
of 1.5% of patients are reported to use homeopathy, with great differ-
ences among nations (range 0.2-8.2%) [9]. Homeopathic medicines
are also used in the treatment of common respiratory infections and
ear-nose-throat ailments [10,11].
A systematic review revealed that antibiotics have no early effect
on pain of acute Otitis Media (OAM) and only a modest effect on the
number of children with tympanic perforations [12]. In this context, a
Cochrane review reported that there is insufcient evidence as to the
effectiveness of antibiotics in preventing recurrent sore throat [13].
There is growing knowledge of the problems of antibiotic side effects
and resistance [14-17].
The homeopathic approach can be advantageous where effective
and safe therapies are not available or not indicated. The majority of
Upper Respiratory Tract Infections (URTI) is caused by rhinoviruses
and antibiotics may provide only modest absolute benets [18,19].
Bacterial infections are rare, supporting the concept that the common
cold is almost exclusively a viral disease [20-22].
AOM is one of the most common diseases of childhood, mostly
between ages 6 and 15 months, and is very often treated with antibiot-
ics but at the earlier stages a mild AOM can be managed with a “wait
and watch” approach [23-27]. Even the effect of systemic corticoste-
roids on important clinical outcomes in AOM remains uncertain [26].
Nowadays, different kinds of therapies for rhinitis are available and,
in this context, one option for treating cold symptoms is with home-
opathy as an adjunctive or rst-line approach [28].
Bellavite P, et al., J Altern Complement Integr Med 2019, 5: 068
DOI: 10.24966/ACIM-7562/100068
HSOA Journal of
Alternative, Complementary & Integrative Medicine
Research Article
Paolo Bellavite1*, Marta Marzotto1 and Beatrice Andreoli2
1Department of Medicine, Section of General Pathology, University of
Verona, Verona, Italy
2Homeopathic Medical School, Verona, Italy
Homeopathic Treatments of
Upper Respiratory and Oto-
rhinolaryngologic Infections:
A Review of Randomized and
Observational Studies
Introduction: Homeopathy is a therapeutic natural medical alterna-
tive that is widely and increasingly being used, even for pediatric pa-
tients. Given this trend, it is essential that clinicians have the resourc-
es to advise their patients as to the potential benets and harms
of this complementary therapy. The aim of this work is to describe
the available literature cited in PubMed concerning the homeopathic
treatments on human subjects (both children and adult) for common
Upper Respiratory Tract Infections (URTI), otitis, rhinitis, sinusitis,
rhinosinusitis, pharyngitis and tonsillitis.
Methods: The PubMed search made use of the keywords “home-
opathy” or “homeopathic”, and the names of the indicated diseases.
The report covers all forms of homeopathic therapy, namely: a) clas-
sical individualized homeopathy, b) ailment-specic medicines and
complexes. In order to take into account the whole mass of literature,
the evidence of the clinical effectiveness is summarized according to
semi-quantitative criteria, based on the number of randomized and
non-randomized papers published in each group of ailments. The
medicines used in the various studies are classied and described.
Results: A total of 40 clinical studies, published until the ends of
2018, which assess the effectiveness of the homeopathic treatment
in one of the abovementioned conditions are reported and classi-
ed. The studies are randomized or equivalence studies with control
group (n=21), non randomized or observational (n=19) and concern
different clinical approaches, namely individualized using high ho-
meopathic dilutions or non-individualized using complex drug formu-
lations. Studies have revealed mixed results, suggesting that some
homeopathic formulations may have signicant effects in URTI and
otorhinolaryngological infections. Several studies have demonstrat-
ed benets to patients’ quality of life and symptom scoring, or equiv-
alence with the conventional medical approach. Scarcity of data and
uncertainty still exists in literature on the effectiveness of individu-
alized approach in URTIs. 21 different medicines were used in a
minimum of two published reports.
Conclusion: Homeopathic formulations in upper respiratory tract
and otorhinolaryngological infections are likely effective and the in-
dividualized approach in non severe otitis is possibly effective. Ho-
meopathic treatments may help when use of antibiotics is not indi-
cated. Due to the heterogeneity of approaches and of drugs used,
additional studies will be required to evaluate the possible integra-
tion of homeopathy into the standard of care for the treatment of
respiratory and otorhinolaryngologic ailments.
Keywords: Homeopathic complex formulations; Homeopathic med-
icines; Homeopathy; Otorhinolaryngologic infections; Upper respira-
tory tract infections
Citation: Bellavite P, Marzotto M, Andreoli B (2019) Homeopathic Treatments of Upper Respiratory and Otorhinolaryngologic Infections: A Review of Random-
ized and Observational Studies. J Altern Complement Integr Med 5: 068.
• Page 2 of 20 •
J Altern Complement Integr Med ISSN: 2470-7562, Open Access Journal
DOI: 10.24966/ACIM-7562/100068
Volume 5 Issue 2 • 100068
A cross-sectional survey conducted in a pediatric otolaryngology
clinic in Israel reported that 32% of parents considered complemen-
tary therapies in their previous or current use and 36% of them used
homeopathy [29]. Evidence sustains its use, due to its greater safety,
speed of improvement and cost savings [30]. An international sur-
vey of acute pediatric tonsillopharyngitis showed that 62% of partic-
ipants used homeopathy and suggested that an integrative approach
may reduce excessive antibiotic prescriptions [31]. Homeopathy is
controversial, but demonstrably safe [32-35]. Consequently, it is im-
portant to provide clear information about the effectiveness of com-
plementary and alternative treatments including homeopathy, through
high-quality studies carried out with a rigorous methodology. Besides
the classic placebo-controlled and randomized trials, for clinical trials
of homeopathy to be accurate representations of practice, we need
more modied approaches that take into account the complexity of
homeopathic intervention [36-38].
Our previous systematic review on the effect of homeopathy in
immunological disorders also included non-peer-reviewed papers
published until 2010, but in this report we have restricted the report
to clinical trials and observational studies cited by PubMed, which
is considered the most important search system of bibliographic re-
sources, also for homeopathy and other CAMs [38-40]. As it is known
(see for example, the scien-
tic merit of a journal’s content is the primary consideration in se-
lecting journals for indexing in PubMed, especially on the explicit
process of external peer review and adherence to ethical guidelines.
The publication of a paper in a journal cited by PubMed is not in itself
a guarantee of quality, but it can be considered an important criterion
of validity, since it is certain that the work was judged by experts in
the eld before is accepted. Therefore, it could be useful to explore in-
formation present in this bibliographic system on the safety and effec-
tiveness of homeopathy in clinical elds in which it is most frequently
used. While acknowledging that additional relevant studies might be
contained in other databases that we have not searched, we present the
overall body of evidence reported in PubMed, showing some techni-
cal details in tables, we discuss the most relevant published papers
and nally we summarize the positive and negative ndings, weight-
ing them according to semi-quantitative criteria.
Since homeopathic medicines are often used in complex formula-
tions, it is interesting to see which medicines occur more frequently
in such formulations and to compare the traditional statements of Ma-
teria Medica with the more modern evidence derived from scientic
Eligibility criteria included all the available literature on human
subjects in the mentioned elds, from 1981 to 2018, published in
Journals included in PubMed, in any language. In this review, all
forms of homeopathic therapy have been included, namely: a) clas-
sical individualized homeopathy, b) ailment-specic medicines and
The initial strategy of the search included all the PubMed papers
with keywords “homeopathy” or “homeopathic” AND suitable oth-
er keywords related to different ailments included in the categories
of URTI and/or otorhinolaryngologic ailments (e.g.,: “homeopathy”
or “homeopathic” AND “infections”). Then, an article had to satis-
fy the following criteria to be included in the analysis: (i) the study
subjects were humans, (ii) the study was original, involved at least
one homeopathic medicine, (iii) sufcient information concerning
study type, number of subjects, diagnosis, treatment (s) and outcomes
was provided. The last search was done on May 21st, 2019. Retrieved
papers were read by two investigators (P. B. and B. A.), who classied
papers according to the type of study and type of homeopathic ap-
proach, then recorded the relevant data concerning number of patients
included and main outcomes. As a part of this step, the study type was
assessed using the following scale: 1a: Randomized Controlled Trial
(RCT) carried out in double-blind conditions; 1b: randomized (open)
controlled study or equivalence study; 2: non randomized controlled
clinical trials, 3: prospective observational study, without control
group; 4: retrospective study of case series. Reviews, single cases and
expert opinions were excluded. Each study was critically evaluated
based on methodology to determine if the approach fullled the in-
clusion criteria. All processes for obtaining and conrming data were
discussed by the team.
Upper Respiratory Tract Infections (URTI) is dened as “An in-
fectious process affecting the upper respiratory tract (nose, paranasal
sinuses, pharynx, larynx, or trachea). Symptoms include congestion,
sneezing, coughing, fever and sore throat.” The 2019 ICD-10-CM
Diagnosis Code J06 (Acute upper respiratory infections of multiple
and unspecied sites) was applied to papers naming “URTI” without
further precise diagnostic criteria? Other papers including the study
of more precise ailments (e.g., tonsillitis, otitis media, etc.) have been
included in the broad categories dened by the disease, without pre-
cise ICD codes, because the original papers did not report them.
The components of the homeopathic medicines have been iden-
tied from the methods of each paper or, if not reported, from the
data sheets and consumer medicine information published by phar-
maceutical companies. A summary of the traditional knowledge of the
medicines used in a minimum of two scientic papers was extracted
by the authors from the generalities of the Boericke Materia Medica
To standardize the nomenclature of medicines, the centesimal (x
100 dilution at each step) and decimal (x 10 dilution at each step)
homeopathic dilutions/dynamizations were here designed as “C” and
“D” respectively, and the numerical grade of dilution. MT means
mother tincture. Where indicated, “High” dilutions were designed as
those that were above the Avogadro-Loschmidt limit, set by conven-
tion at C12 or D24.
Using keywords “homeopathy” or “homeopathic”, 6506 papers
were retrieved. Most of these papers were excluded from analysis
since they concerned basic research, reviews, discussions, or ailments
not included in the topics of this study. In fact, adding further key-
words to the search, the following number of papers was retrieved:
Homeopathy OR homeopathic AND “infections” = 310; AND “rhini-
tis” = 96, AND “URTI” = 17, AND “otitis” = 43, AND “pharyngitis”
= 13, AND “tonsillitis” = 12, AND “common cold” = 28, AND “si-
nusitis” = 29, AND “rhinosinusitis” = 9. After excluding duplicates
in these different searches and reading the papers, according to the
topics and criteria described in Methods, 40 different papers were re-
trieved and included in this review.
The papers included in the review, with methodologic details and
main outcomes, are reported in table 1, in chronologic order.
Citation: Bellavite P, Marzotto M, Andreoli B (2019) Homeopathic Treatments of Upper Respiratory and Otorhinolaryngologic Infections: A Review of Random-
ized and Observational Studies. J Altern Complement Integr Med 5: 068.
• Page 3 of 20 •
J Altern Complement Integr Med ISSN: 2470-7562, Open Access Journal
DOI: 10.24966/ACIM-7562/100068
Volume 5 Issue 2 • 100068
Author and year Study type
N. of subjects Conditions (diagnosis) Treatment (s) Outcomes Key results Ref.
Gassinger 1981 1b 53 Acute rhinitis Eupatorium perfoliatum vs.
aspirin Symptoms severity score Equivalence between home-
opathy and allopathy [42]
Maiwald 1988 1b 170 Acute rhinitis Homeopathic complex Grip-
pheel vs. aspirin Symptoms severity score Equivalence between home-
opathy and allopathy [43]
de Lange de
Klerk 1994 1a 170 children URTI Individualized vs. placebo
Frequency, duration and
se-verity of rhinitis,
pharingytis episodes
Little, not signicant, effect
of ho
meopathy vs. placebo
Friese 1997 2 131 children AOM Individualized vs. allopathy Duration of pain and
Homeopathy slightly better
than con-
ventional therapy
Wiesenauer 1998 3 107 Acute tonsillitis
Low-dilution homeopathic
complex of Phytolacca amer-
icana, Guajacum ofci-
nale, Capsicum annuum
Subjective and objective
Decrease of symptoms in
most patients (uncontrolled) [46]
Adler 1999 3 11 9 Acute sinusitis Homeopathic complex
Sinusitis PMD Symptoms Trend to positive (uncon-
trolled) [47]
Rau 2000 3 48 both adults
and children Acute tonsillitis
Complex of Phytolacca
americana, Guajacum ofci-
nale, Capsicum annuum
Decrease of symptoms in
most patients (uncontrolled)
with no adverse effects
Frei 2001 3 230 children AOM Individualized Individualized
Improvement in 39% of pa-
tients after 6 h, another 33%
after 12 h (uncontrolled)
Riley 2001 2 456 URTI Individualized homeopathy
vs. allopathy
Healing or a major im-
provement after 14 days of
treatment, adverse effects
Improvement in 82.6% of
homeopathic patients, 68% of
Jacobs 2001 1a 75 children AOM Individualized vs. placebo Treatment failure and
symptoms score
Less failure in verum group,
not signicant; little and
signicant decrease of symp-
toms in verum group
Rabe 2004 2 485 URTI
Homeopathic complex
rippheel vs. anti-inammato-
ry agents
Symptoms Equivalence between home-
opathy and allopathy [52]
2005 2 739 Rhinitis and sinusitis
Low-dilution homeopathic
complex formulation Eu-
phorbium compositum, nasal
spray vs. xylometazoline
Symptoms and tolerability Equivalent efcacy [53]
2005 (a) 1a 251 children URTI Parents-selected homeopathic
medicines vs. placebo
Prevention of new epi-
sodes, symptoms scores
No effectiveness of homeop-
athy over placebo [54]
2005 (b) 1b 169 children URTI Individualized vs. conven-
tional care Symptoms score
Decrease of days with
symptoms in
homeopathic group
2005 4 499 children Acute rhinopharingitis
Homeopathic strategy vs.
allopathic strategy (e.g.
Number of episodes,
quality of life, costs
Various indices signicantly
in favor
of homeopathic strategy,
lower medical costs (case
series, uncontrolled)
2006 3 397 Acute rhinitis
Homeopathic complex
Engystol vs. conventional
General and local symp-
Homeopathic medicine
equivalent to the convention-
al treatment
2007 1a 208 children URTI Individualized vs. parents-se-
lected medicines
Prevention of new
symptoms scores
No difference between the
two methods of prescription [58]
2007 2 1557 URTI
Homeopathic strategy vs.
allopathic (e.g.
anti-inammatory drugs,
Healing or major improve
ment after 14 days of
Homeopathic treatment not
inferior to the allopathic and
best tolerated
Zabolotnyi 2007 1a 113 Maxillary sinusitis Homeopathic complex
Sinfrontal vs placebo Symptoms Signicant improvement over
place bo [60]
Kneis 2009 1a 113 Maxillary sinusitis
Homeopathic complex
Sinfrontal vs placebo and vs
Cost savings
Signicant cost savings
comparing both with placebo
and antibacterials [61]
Witt 2009 3 134 Chronic sinusitis Individualized Symptoms, quality of life
Major improvement per-
sisting at
least 2 years (not controlled)
Ramchandani 2010 3 30 children URTI Individualized
Number of episodes during
6 months before and after
Decrease of episodes after
homeopathic treatment [63]
Citation: Bellavite P, Marzotto M, Andreoli B (2019) Homeopathic Treatments of Upper Respiratory and Otorhinolaryngologic Infections: A Review of Random-
ized and Observational Studies. J Altern Complement Integr Med 5: 068.
• Page 4 of 20 •
J Altern Complement Integr Med ISSN: 2470-7562, Open Access Journal
DOI: 10.24966/ACIM-7562/100068
Volume 5 Issue 2 • 100068
Taylor 2011 1a 119 children AOM
Standard therapy alone vs
standard therapy plus homeo-
pathic ear drops
Lower symptoms and faster
improvement in children
receiving ear drops
Bernstein 2011 1a 42 Nonallergic rhinitis
Homeopathic complex Sinus
Buster (Capsicum annum and
Eucalyptol) vs placebo
Symptoms Improvement of symptoms [65]
Sinha 2012 1a 81 AOM Individualized homeopathy
vs conventional treatment
Symptoms and tympanic
membrane examination
over 21 days
No signicant differences;
quicker improvement and
less use of antibiotics in
homeopathy group
Nayak 2012 3
628 both
children and
Chronic sinusitis Individualized homeopathy Symptoms and X-ray
Highly signicant improve-
ment [67]
Taylor 2014 1a 206 children AOM Antibiotic vs antibiotic plus
homeopathic ear drops
Filling of antibiotic during
the follow-up
Less antibiotic use in children
treated with homeopathic
ear drops
Zanasi 2014 1a 80 URTI
Homeopathic complex Stodal
(Anemone pulsatilla, Rumex
crispus, Bryonia dioica,
Ipecacuanha, Spongia tosta,
Sticta pulmunaria, Antimoi-
um tartaricum, Myocarde,
Coccus cacti, Drosera) vs
Cough severity and sputum
Improvement of clinical
parameters [69]
Grimaldi Bensouda
2014 3 518 (on 8559) URTIs Homeopathic prescription vs
conventional prescription Clinical
Less use of antibiotics and
drugs in people treated with
homeopathy alone ore ho-
meopathy plus conventional
Malapane 2014 1a 30 children Acute viral tonsillitis
Homeopathic complex
Tonzolyt (Atropa belladonna,
Calcarea phosphorica, Hepar
sulphur, Kalium bichromium,
Kalium muriaticum, Mercu-
rius protoiodid, Mercurius
biniodid) vs placebo
Signs and symptoms and
intensity of pain
Improvement of symptoms
and pain [71]
Michalsen 2015 3
1050 both
adults and
Viral rhinitis Homeopathic complex
Contramutan N Saft
Safety and effectiveness of
the product
Safety and effectiveness both
in adults and children [72]
Zanasi 2015 3 85 children URTI
Homeopathic syrup (Stodal)
vs homeopathyc syrup plus
Symptoms and adverse
side effects
Equal reduction of symp-
toms; more adverse side
effects in the second group
Thinesse Mallwitz
2015 1b
523 both
and adults
Standard treatment alone
vs standard treatment plus
homeopathic complex
Inucid (Aconitum, Bryonia,
Eupatorium perfoliatum,
Gelsemium, Ipecacuanha,
and Phosphorus)
Less use of symptomatic
medications, earlier improve-
ment of symptoms and better
tolerability in the second
Beghi 2016 4 459
Respiratory tract
infections (not
Oscillococcinum vs no
treatment Clinical Reduction of respiratory in-
fection episodes during time [75]
Jong 2016 1b 200 children URTI
Homeopathic complex
CalSuli-4-02 (Calcium
carbonicum, Calcium uo-
ratum, Calcium phospho-
ricum, Sulphur iodatum)
vs homeophathic complex
(Gentiana, Aconitum, Brynia,
Ferrum phosphoricum,
Acidum sarcolacticum)
Symptoms, treatment satis-
faction, antibiotic use,
safety, tolerability
Comparable reduction of
symptoms and antibiotic use;
better treatment satisfac-
tion and tolerability with
Pedrero Escalas
2016 1a 97 Otitis media with
Aerosol standard therapy
(mucolytic and steroids) plus
placebo vs aerosol standard
therapy plus homeopathic
PNO examination and
No signicant differences
and similar adverse effects [77]
Van Haselen 2016 1b 261 children URTI
Standard treatment alone
vs standard treatment plus
homeopathic complex In-
Symptoms and fever
Less use of symptomatic
medications and earlier im-
provement of symptoms and
fever in the second group
Citation: Bellavite P, Marzotto M, Andreoli B (2019) Homeopathic Treatments of Upper Respiratory and Otorhinolaryngologic Infections: A Review of Random-
ized and Observational Studies. J Altern Complement Integr Med 5: 068.
• Page 5 of 20 •
J Altern Complement Integr Med ISSN: 2470-7562, Open Access Journal
DOI: 10.24966/ACIM-7562/100068
Volume 5 Issue 2 • 100068
Randomized Trials of Individualized Homeopathy
De Lange and coworkers carried out a double-blind, randomized
study which they used to evaluate the frequency, duration and severity
of rhinitis, pharyngitis and tonsillitis in a group of children [44]. The
homeopathic prescription included “constitutional” medicines for
preventive purposes and medicines for the treatment of acute phases.
The year-long therapy was continuously adjusted on an individual ba-
sis, and the data was collected by means of diaries kept by the parents
and at-tending physicians. The results showed that the homeopathic
therapy was slightly but not signicantly better than the placebo: the
mean number of infective episodes was 7.9/year in the treated group
and 8.4/year in the control group. The children in the active group
experienced episodes that were generally shorter and less severe; the
percentage of children not requiring antibiotics was 62% vs. 49% in
homeopathy and conventional therapy respectively. The authors con-
cluded that the differences between the two treatments were interest-
ing but small (odds ratio favoring homeopathy versus placebo: 1.67,
95% CI: 0.96-28.9).
A randomized double-blind placebo controlled pilot study was
carried out on children with otitis media [51]. Subjects presenting
middle ear effusion and ear pain and/or fever for no more than 36
h were enrolled in the trial. They received either an individualized
homeopathic medicine or a placebo; administered orally three times
daily for 5 days or until symptoms subsided. The 4 most common-
ly medicines prescribed included Pulsatilla, Chamomilla, Sulphur
and Calcarea carbonica. Outcome measures included the number of
treatment failures after 5 days, 2 weeks and 6 weeks. Diary symptom
scores during the rst 3 days and middle ear effusion at 2 and 6 weeks
after treatment were also evaluated. There were fewer treatment fail-
ures in the group receiving homeopathy after 5 days, 2 weeks and 6
weeks. However these differences were not statistically signicant.
Diary scores showed a signicant decrease in symptoms at 24 and 64
h after treatment, in favor of homeopathy (P < 0.05).
In summary, randomized trials of individualized homeopathy are
few and the results are conicting, thus preventing any possible con-
Randomized Trials of Ailment Specic Formulations
Although people are best treated with an individualized medicine
chosen by a professional homeopath, the use of complex homeopathic
medications is very popular essentially because it is easier to match
the drug with the symptoms of the disease. A series of medicines for
non allergic rhinitis, prepared from various combinations of Luffa
opercolata, Kalium bichromicum and Cinnabaris (in low homeopath-
ic dilutions) were compared with a placebo in a double-blind trial
[83]. Criteria for the therapeutic result were headache, blocked nasal
breathing, trigeminal tenderness, reddening and swelling of nasal mu-
cosa and postnasal secretion. All combinations were ineffective in the
treatment of those sinusitis symptoms. The author’s conclusion was
that, unless other data emerge from a study of individualized homeo-
pathic prescriptions (“repertorisation”), the drugs should not be con-
sidered active in acute or chronic sinusitis in the general population.
They also point out that similar negative results have been obtained
with antibiotics, nasal decongestants and drainage of the nasal cavi-
Sinfrontal is a complex homeopathic medication (containing Cin-
nabaris 4D, Ferrum phosphoricum 3D, Mercurius solubilis 6D) that
is used for a variety of upper respiratory tract infections and has shown
promise as a treatment for rhinosinusitis. A prospective, randomized,
double-blind, placebo-controlled trial, carried out in Ukraine, investi-
gated the efcacy of this complex homeopathic medication compared
to a placebo, in patients with maxillary sinusitis [60]. Fifty-seven pa-
tients received Sinfrontal and 56 patients received placebo. Between
day zero and day seven, Sinfrontal produced a signicant reduction
in the total symptom score compared to the placebo (p < 0.0001). Af-
ter three weeks, 68.4% patients on active medication had a complete
remission compared with 8.9% of placebo patients. Eight adverse
events were reported, assessed as being of mild or moderate intensity.
The authors suggest that this complex homeopathic medication is safe
and appears to be an effective treatment for acute maxillary sinusitis.
A cost-utility analysis based on data from this trial calculated that
Sinfrontal led to incremental savings of €275 per patient compared
with the placebo over 22 days, essentially due to markedly reduced
absenteeism from work [61].
Table 1: Homeopathic clinical studies in the elds of infections of upper airways and ear-nose-throat ailments.
aClinical trial: 1a: double-blind randomized controlled; 1b: non-blinded randomized (open) controlled or equivalence study; 2: non randomized controlled clinical trial; 3: prospec-
tive observational study, without control group; 4: retrospective study of case series.
Jacobs 2016 1a 154 children URTI
Homeopathic complex
(Allium Cepa, Hepar Sulph
Calc, Natrum Muriaticum
Phosphorous, Pulsatilla,
Sulphur, Hydrastis)vs placebo
Symptoms severity (Runny
nose, Sneeze, Cough, Con-
No immediate relieving
effect, improvement in
composite symptoms score,
especially in the rst day of
Palm 2017 1b 256 Moderate recur-
rent tonsillitis
Standard symptomatic
treatment alone vs standard
symptomatic treatment plus
homeopathy complex Sil-Al-
Mean time period between
consecutive ATI
Lower risk of ATI in patients
treated also with homeopathy [80]
Voss 2018 1b 89 children URTI
Homeopathic complex (Dro-
sera, Coccus Cacti, Cuprum
sulphuricum, Ipecachuana)
vs placebo
Clinical Improvement of symptoms
and equal tolerability [81]
Allaert 2018 3 414 children URTI
Management of cough with
two homeopathic syrups
or with allopathic drugs by
Cough disappearance and
patient satisfaction
Better improvement with
homeopathic syrups and
same satisfaction
Citation: Bellavite P, Marzotto M, Andreoli B (2019) Homeopathic Treatments of Upper Respiratory and Otorhinolaryngologic Infections: A Review of Random-
ized and Observational Studies. J Altern Complement Integr Med 5: 068.
• Page 6 of 20 •
J Altern Complement Integr Med ISSN: 2470-7562, Open Access Journal
DOI: 10.24966/ACIM-7562/100068
Volume 5 Issue 2 • 100068
A randomized, double-blind, parallel trial was carried out in 2011
to investigate the efcacy and safety of ICX72, or “Sinus Buster”, a
proprietary homeopathic preparation of Capsicum annum 3D (chili
pepper) and Eucalyptol, versus placebo administered continuously
over 2 weeks in subjects with nonallergic rhinitis [65]. In this trial,
two kinds of endpoints were established: the primary one was the
change in Total Nasal Symptom Scores (TNSS) from baseline to
end of study, then the secondary ones included changes in Individual
Symptom Scores (ISS) over 2 weeks and average time to rst relief.
Authors recorded mean TNSS and ISS after single dosing at different
intervals over 60 minutes and they analyzed rhinitis quality of life,
rescue medication and safety endpoints. The study has shown signi-
cant differences in changes from baselines to the end of the study for
both TNSS and ISS parameters. Patients treated with ICX72 report-
ed an improvement in nasal congestion, sinus pain, sinus pressure,
and headache at 5, 10, 15 and 30 minutes, persisting at 60 minutes
for nasal congestion and sinus pain (P < .05). In addition, there were
no differences in adverse side 14 effects, rescue medication, rebound
congestion or impaired olfaction at the end of the study when com-
pared with placebo patients. They concluded that intranasal capsaicin,
when used continuously over 2 weeks, rapidly and safely improve
symptoms in non-allergic rhinitis subjects. Interestingly, in this ther-
apeutic context Capsicum annum can be seen as working according
the traditional “similia” rule, or “hormesis” concept in modern terms
[84-86]. In fact its active principle is capsaicin, a strongly irritating
compound whose initial receptor excitation is followed by a refracto-
ry period. The use of low doses exploits the rebound reaction utiliz-
ing the long-lasting refractory period to decrease mucosal irritation
and related symptoms. Recently the use of capsaicin in non-allergic
rhinitis has also been suggested in non-homeopathic literature and a
Cochrane review has suggested that capsaicin may be an option for
alleviating the symptoms of idiopathic non-allergic rhinitis [87,88].
A randomized trial was carried out to assess the effectiveness of a
homeopathic ear drop for treatment of otalgia in children with acute
otitis media [64]. Patients were 120 children aged from 6 months to
11 years old, diagnosed with AOM, tympanic membrane (s) distinctly
abnormal and signicant discomfort. Exclusion criteria were a chron-
ic medical condition, a treatment with antibiotics within the previous
2 days or with homeopathic medicine during the previous 30 days, a
diagnosis of AOM received during the preceding 30 days or a perfo-
rated tympanic membrane. Every patient, after the enrollment phase,
received an immediate prescription for an oral antibiotic, or a delayed
antibiotic prescription, as well as treatments for otalgia such as acet-
aminophen, ibuprofen, or topical benzocaine ear drops. In addition to
these, the severity of the child’s AOM at presentation was assessed
using (a) the “Otoscopy Scale” (OS-8), after which only children with
an OS-8 score of ≥4 were eligible for the study and (b) parental rating
of symptoms using the faces scale, after which only children whose
parents indicated that the symptom severity was 4 or greater (corre-
sponding to a ‘moderate problem’ or more) were eligible for the study.
At enrollment, patients were randomized by a computer to standard
therapy alone or standard therapy plus homeopathic ear drops named
Hy-lands Earache Drops® (containing a combination of six medi-
cines: Pulsatilla, Chamomilla, Sul-phur, Calcarea carbonica, Bella-
donna and Lycopodium, all in the 30C potency range). Ear drops were
administered in the following way: 3-4 drops up to 3 times/day, as
needed for relief of AOM symptoms for a maximum of 5 days. Com-
pared to children receiving standard therapy alone, those who also
received ear drops had faster symptom relief, with signicantly mild-
er symptoms at the second and third assessments, which approximate-
ly correspond to the period of 24-36 h after the diagnosis of AOM,
suggesting that homeopathic ear drops may be most effective in the
early period after a diagnosis of AOM and could possibly reduce the
use of delayed antibiotics. This trial concluded that homeopathic ear
drops are moderately effective in treating otalgia in children with
AOM and that they may be most effective in the early period after a
diagnosis of AOM.
A further randomized trial was conducted on a pediatric popula-
tion of 206 children aged from 6 months to 11 years, with diagnosis
of AOM and managed with a delayed antibiotic approach [68]. They
were randomized to receive homeopathic ear drops plus standard
therapy or standard therapy alone. Only 26.9% of children of the “ho-
meopathy group” received antibiotic therapy, versus 41.2% of chil-
dren randomized in the other group (P=0.032). Based on this data, the
authors suggested that homeopathic ailment specic therapies may
be helpful in reducing the prescriptions of antibiotics in children with
A single-center, randomized, double-blind, placebo-controlled
clinical trial was published in 2014 to test the efcacy of a homeo-
pathic syrup in treating cough, due to non-complicated URTI in adults
[69]. The administered homeopathic syrup was Stodal® composed
by Anemone pulsatilla 6C, Rumex crispus 6C, Bryonia dioica 3C,
Ipecacuanha 3C, Spongia tosta 3C, Sticta pulmonaria 3C, Antimo-
nium tartaricum 6C, Myocarde 6C, Coccus cacti 3C, Drosera MT.
Patients were treated with the homeopathic syrup or with a placebo
(using a computer program to generate block randomization) for a
week; they recorded cough severity in a diary for two weeks and their
sputum viscosity was assessed with a viscosimeter before and after 4
days of treatment and by a subjective evaluation of it. Patients were
instructed to take a dose of 15 ml, four times a day for 7 days, then
cough severity was measured by a validated verbal category-descrip-
tive score. Overall, 80 patients were enrolled, 40 were randomized
to the homeopathic group and 40 were randomized to the placebo
group. In the rst four days of treatment the mean severity of cough
decreased from score 4 (indicating serious coughing, very frequent
and interfering with normal daily life or sleep) to 2 (indicating some
short periods of cough, without much hardship) in the homeopathic
group and remains greater than score 3 (indicating frequent coughing)
in the other one. Viscosity was signicantly lower in the homeopathic
group (p = 0.018). The subjective evaluation was not signicantly
different between the two groups (p = 0.059). No adverse side effects
were reported. Authors concluded that the homeopathic syrup admin-
istered in the study was able to effectively reduce cough severity and
sputum viscosity.
A randomized, double-blind, placebo-controlled, 6-day pilot study
was carried out to determine the efcacy of an homeopathic com-
plex on the symptoms of acute viral tonsillitis in African children in
South Africa [71]. Acute viral tonsillitis is a very common medical
condition in school-aged children. This study enrolled 30 children
aged from 6 to 12 years old, complaining of viral tonsillitis, from a
primary school in Gauteng. They were treated with a homeopathic
complex, two table spoonfuls four times daily, or with a placebo. The
homeopathic complex (“Tonzolyt”) was com-posed as follows: Atro-
pa belladonna 4D, Calcarea phosphoricum 4D, Hepar sulphuris 4D,
Kalium bichromat 4D, Kalium muriaticum 4D, Mercurius protoiodid
Citation: Bellavite P, Marzotto M, Andreoli B (2019) Homeopathic Treatments of Upper Respiratory and Otorhinolaryngologic Infections: A Review of Random-
ized and Observational Studies. J Altern Complement Integr Med 5: 068.
• Page 7 of 20 •
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DOI: 10.24966/ACIM-7562/100068
Volume 5 Issue 2 • 100068
10D, and Mercurius biniodid 10D. In 16 the study the intensity of pain
was measured with a Pain Rating Scale and changes in tonsillitis signs
and symptoms were assessed with a Symptom Grading Scale. Results
shown that there were signicant differences between the groups in
pain associated with tonsillitis, pain in swallowing, erythema and in-
ammation of the pharynx and tonsil size. Authors concluded that
the administered complex exhibited signicant anti-inammatory and
pain-relieving qualities in children with acute viral tonsillitis and that
a larger, more inclusive research study should be undertaken to verify
the ndings of this study.
A randomized, controlled, multinational clinical trial analyzed the
effectiveness of homeopathic treatment in URTI [74]. A population of
523 patients aged 1 to 65 years old was treated with on-demand symp-
tomatic standard treatment or homeopathic medication (Inucid) to-
gether with the same treatment. Inucid tablets, containing a xed
combination of 6 homeopathic single substances (Aconitum 3D, Bry-
onia 2D, Eupatorium perfoliatum 1D, Gelsemium 3D, Ipecacuanha
3D and Phosphorus 5D), were administered to children in the ho-
meopathic group for a period of 7 days (8 tablets/day during the rst
72 hours, 3 tablets/day during the following 96 hours). Paracetamol
syrup, ambroxol syrup, and oxymetazoline nasal spray were offered
as symptomatic standard medication to all children on an “as-need-
ed” basis. The most important outcome measure was the response at
day 4 (absence of fever and absence or very mild symptoms). The
conclusion was that homeopathic treatment shortened URTI duration,
reduced the use of symptomatic medication and was well tolerated.
A randomized, controlled, multinational clinical trial analyzed
the clinical effectiveness of a homeopathic medicine in 261 children
affected by URTI [78]. Patients were divided in two groups: both re-
ceived on-demand symptomatic standard treatment but only one re-
ceived a homeopathic therapy with the above-mentioned formulation
Inucid. This medicine, used as add-on treatment in pediatric URTI,
reduced global disease severity, shortened symptom resolution, and
was safe to use.
A study conducted in 2016 analyzed the treatment of cold symp-
toms (runny nose, cough, congestion and sneezing ) in young chil-
dren, using an homeopathic syrup or a placebo Tested medicine was
“Cold‘n’ Cough for Kids, composed by Allium Cepa 6D, Hepar Sul-
phuris 12D, Natrum Muriaticum 6D, Phosphorus 12D, Pulsatilla 6D,
Sulphur 12D, Hydrastis 6D [79]. Enrolled patients were aged from
2 to 5 years old and they were randomized in two groups (treatment
or placebo). Therapy was administered by parents, according to the
assessment of the severity of each symptom. Results show there was
no signicant difference in improvement one hour after the dose for
any symptom between the two groups (primary outcome), but in the
course of the rst day the severity of cold symptoms decreased faster
among those receiving the cold syrup, when compared to placebo re-
A prospective randomized, double blinded interventional placebo
control study was conducted to assess the effectiveness of homeopa-
thy in the treatment of Otitis Media with Effusion (OME) in children
[77]. Homeopathy was not used alone, but as an adjuvant treatment,
with aerosol therapy (mucolytics and corticosteroids). Children treat-
ed with homeopathy received a homeopathic complex (Agraphis
nutans 5C, Thuya Occidentalis 5C, Kalium muriaticum 9C and Ar-
senicum iodatum 9C), and this protocol did not result in being an
effective adjuvant in children with OME who had already received
aerosol therapy, including mucolytics and corticosteroids.
A controlled, pragmatic, randomized clinical trial evaluated the ef-
fectiveness and safety of a homeopathic complex called SilAltro-5-90,
administered together with conventional symptomatic therapy, in the
treatment of recurrent tonsillitis [80]. SilAtro-5-90 is a complex ho-
meopathic medicinal product containing Atropinum sulfuricum 5D,
Mercurius bijodatus 8D, Hepar sulfuris 3D, Ka-lium bichromicum
4D, Silicea 2D. Authors enrolled 256 patients and randomized them
into two groups: one was treated with standard therapy alone and the
other with both allopathic and homeopathic medicines (standard ther-
apy plus SilAltro-5-90). Second group showed a signicantly lower
risk of getting an ATI over time, with a reduction in tonsillitis symp-
toms and need for antibiotics.
Another randomized, placebo-controlled clinical trial studied the
effect of an homeopathic complex (“Monapax”) composed of low di-
lutions of Drosera TM, Coccus cacti 1D, Cuprum sulfuricum 4D and
Ipecacuanha 4D which are some medicines that include the cough
in their clinical indications [81]. The trial was conducted in a pediat-
ric population, composed of 89 children from 5 months to 12 years
of age. The improvement in children receiving the verum and not
the placebo resulted in being statistically signicantly higher, with
non-inferior tolerance.
In summary, randomized trials of ailment-specic formulations
are 5 for URTI and 7 for otorhino-laryngological infections, consti-
tuting a body of predominantly positive results.
Equivalence Trials of Individualized Homeopathy
Friese and coworkers reported studies comparing the results ob-
tained in otitis media in children, treated using two different medi-
cal approaches: a) classical homeopathic medicines (e.g., Aconitum,
Apis, Belladonna, Lachesis, Pulsatilla, Silicea, Lycopodium, Chamo-
milla and Capsicum) prescribed after an individual homeopathic case
analysis (repertorisation), b) conventional therapy based on antibi-
otics, mucolytics and antipyretics [45,89,90]. The mean duration of
pain was two days in the homeopathic group and three days in the
conventional therapy group (n.s.) and the duration of therapy was four
and ten days respectively. The latter difference was statistically sig-
nicant (p<0.01). By following-up the children for six weeks, in the
homeopathic group, 70.7% of the children who completed the study
did not experience any recurrence; in the allopathic group, 64% of
the children completing the study remained relapse free (n.s.). The
average duration of pain in the two groups was respectively three days
and four days (n.s.). Therefore, this study suggested a similar effec-
tiveness of the homeopathic and conventional treatments.
An interesting multi-centre, prospective, observational study in a
real-world medical setting compared the effectiveness of homeopa-
thy with that of conventional medicine [50]. 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
conditions: upper respiratory tract complaints, lower respiratory tract
complaints, ear complaints. The response to treatment (healing or a
major improvement after 14 days of treatment) was 82.6% among the
patients receiving homeopathy and 68% among those receiving con-
ventional medicine. The rate of adverse side effects in the convention-
al therapy group was 22.3%, versus 7.8% for the homeopathy group.
Since the trial was not randomized, no statistical comparisons could
be made between groups. In any case, the authors suggest that home-
opathy appeared to be at least as effective as conventional medical
Citation: Bellavite P, Marzotto M, Andreoli B (2019) Homeopathic Treatments of Upper Respiratory and Otorhinolaryngologic Infections: A Review of Random-
ized and Observational Studies. J Altern Complement Integr Med 5: 068.
• Page 8 of 20 •
J Altern Complement Integr Med ISSN: 2470-7562, Open Access Journal
DOI: 10.24966/ACIM-7562/100068
Volume 5 Issue 2 • 100068
care in the treatment of patients with these three conditions. A repli-
cation of this study was carried out as an international, multicentre,
comparative cohort study of non-randomized design [59]. Therapeu-
tic outcomes were measured in terms of the response rate, dened as
the proportion of patients experiencing ‘complete recovery’ or ‘major
improvement’ in each treatment group. The full analysis evaluated
data for 1577 patients, out of which 857 received homeopathic (H)
and 720 conventional (C) treatments. The majority of patients in both
groups reported their outcomes, after 14 days of treatment, as either
complete recovery or major improvement (p = 0.0003 for non-infe-
riority testing). The response rates after 7 and 28 days also showed
no signicant differences between the two treatment groups. Howev-
er, onset of improvement within the rst 7 days after treatment was
signicantly faster for the homeopathic treatment in both children (p
= 0.0488) and adults (p = 0.0001). Adverse drug reactions occurred
more frequently among adults in the conventional group than in the
homeopathic group (C: 7.6%; H: 3.1%, p = 0.0032), whereas in chil-
dren the occurrence of adverse drug reactions was not signicantly
A pragmatic, randomized, equivalence trial was performed by
Steinsbekk and coworkers, investigating whether individualized
treatment by a homeopath is effective in preventing childhood upper
respiratory tract infections [55]. Children recruited via mailed letters,
from a group previously diagnosed with upper respiratory tract infec-
tions, were randomly assigned to receive either homeopathic care or
conventional health care for 12 weeks. There was a signicant differ-
ence in the median total symptom score in favor of homeopathic care
(24 points) compared to the control group (44 points) (p = 0.026).
The number of days with symptoms was 8 and 13 for the homeo-
pathic and reference groups respectively (p = 0.006). Negative results
were obtained by the same group in a double-blind placebo controlled
randomized trial investigating the effect of self treatment with one of
three self selected homeopathic medicines for the prevention of child-
hood upper respiratory tract infections [54]. A large group of children,
recruited by post from those previously diagnosed with upper respira-
tory tract infections, were randomly assigned to receive either placebo
or highly diluted medicines, administered twice weekly for 12 weeks.
Parents chose the medicine based on simplied constitutional indica-
tions. No difference was found between the frequency and scores of
infection of the two groups. In a further study, the same group of re-
searchers compared homeopathic care (individual homeopathic con-
sultations with any medicine in any potency being prescribed) to self
treatment with one of three self-prescribed medicines in 30c dilution,
administered twice weekly, for 12 weeks [58]. The results indicated
that there were no signicant differences in clinical effects between
the two types of homeopathic therapy for symptoms scores of upper
respiratory tract infections.
Another study compared the effectiveness and costs of two treat-
ment strategies (‘homeopathic strategy’ vs. ‘antibiotic strategy’) used
in routine medical practice by allopathic and homeopathic GPs in the
treatment of recurrent acute rhinopharyngitis in children [56]. Data
from a large set of patients, clinically observed for 6 months, was
analyzed and grouped according to the type of drug prescribed and the
episodes of acute rhinopharyngitis, complications, and adverse side
effects. The results showed that the ‘homeopathic strategy’ yielded
signicantly better results than the ‘antibiotic strategy’ in terms of
the number of episodes of rhinopharyngitis (2.71 vs. 3.97, p < 0.001),
number of complications (1.25 vs. 1.95, p < 0.001), and quality of life
(global score: 21.38 vs. 30.43, p < 0.001), with lower direct medical
costs in favor of homeopathy (€88 vs. €99, p < 0.05). The authors sug-
gest that homeopathy may be a cost-effective alternative to antibiotics
in the treatment of recurrent infantile rhinopharyngitis.
A nationwide survey of primary care practice was conducted in
a representative sample of General Practitioners (GPs) from across
France and their patients between 2007 and 2008 [70]. Objectives
were to describe and compare antibiotic and antipyretic/anti-inam-
matory drugs use, URTI symptoms’ resolution and occurrence of po-
tentially-associated infections in patients seeking care from General
Practitioners (GPs) who exclusively prescribe Conventional Medi-
cations (GP-CM), or who regularly prescribe homeopathy within a
mixed practice (GP-Mx), or who are certied homeopathic GPs (GP-
Ho). The study was organized with three follow-up interviews, at one,
three and twelve months. Consumption of antibiotics and antipyretic/
anti-inammatory drugs for URTI was dened as the proportion of
patients who used at least one drug from a denite list. Use of antibi-
otics and antipyretic/anti-inammatory drugs was dened as at least
one usage for URTI. Resolution of the URTI was dened by self-re-
porting of complete resolution or signicant improvement of baseline
symptoms. Infections potentially associated with URTI were dened
by self-reporting of at least one declaration of a diagnosis of otitis
media, otitis externa or sinusitis (with or without treatment). The sur-
vey enrolled 825 GPs and 8,559 patients: 518 of the patients agreed
to partecipate and responded to all three follow-up interviews and
therefore were included in the analysis. Most communal complaints
were rhinopharyngitis (73.9%), bronchitis (28.0%), u-like symp-
toms (12.7%), Strep-A negative viral angina (8.7%) and bronchiolitis
(5.2%). Generally, patients suffering from URTI who choose a GP-Ho
used half the amount of antibiotics and antipyretic/anti-inammatory
drugs, when compared to patients choosing a conventional medicine
practitioner. No difference in the resolution of the URTI symptoms
was observed between groups, but there was a lack of statistical va-
lency for this outcome. No difference was seen in patients from the
GP-Mx group, which was comparable to the GP-CM group in all out-
comes [70].
A pilot study, randomized placebo-controlled parallel group, was
conducted at Regional Research Institute of Homeopathy, Jaipur,
(Rajasthan), India of CCRH from May 2009 to April 2010 [66]. It
compared the effectiveness of Homeopathy and Conventional ther-
apy in AOM. Patients were randomized by a computer and receive
individualized homeopathic medicines or conventional treatment.
Homeopathic medicines were administered in Fifty Millesimal (LM)
potencies and Medicines were selected after repertorization with
CARA Software. Medicines which were used were Pulsatil-la nig-
ricans, Mercurius solubilis, Silicea, Chamomilla, Lycopodium clava-
tum and Sulphur. Conventional treatments included analgesics, anti-
pyretics and anti-inammatory drugs. Patients who did not improve
were treated with antibiotics on the third day and the secondary objec-
tive of the trial was to evaluate how many patients required antibiotic
treatment in both groups. Outcomes were assessed over 21 days by a
scale called AOM-Severity of Symptoms and by tympanic membrane
examination. Patients were 81 children of both sexes, between 2 and 6
years of age, suffering from earache of not more than 36 hours’ dura-
tion and with tympanic membrane bulging and loss of landmarks. 80
patients completed follow-up, 40 for conventional and 40 for homeo-
pathic treatment. In the rst group, 100% of patients were cured, in
the second group, 95% were cured while 5% were lost to the last two
Citation: Bellavite P, Marzotto M, Andreoli B (2019) Homeopathic Treatments of Upper Respiratory and Otorhinolaryngologic Infections: A Review of Random-
ized and Observational Studies. J Altern Complement Integr Med 5: 068.
• Page 9 of 20 •
J Altern Complement Integr Med ISSN: 2470-7562, Open Access Journal
DOI: 10.24966/ACIM-7562/100068
Volume 5 Issue 2 • 100068
follow-up. By the third day of treatment, in the rst group one patient
was cured while in the second one, four patients were cured. In the
rst group, 97.5% of patient’s required antibiotics but no antibiotics
were required in the homeopathic group. The study results showed
that conventional and homeopathy medicines are equally effective in
the treatment of AOM [66]. Furthermore, homeopathic medicines did
not have side effects. Results showed that in acute conditions home-
opathy can act fast and that individualized homeopathy can reduce or
avoid use of antibiotic in children with diagnosis of AOM.
A letter published in 2012 commented on Sinha’s trial, which
showed the effectiveness of homeopathy in treating AOM [66,91].
The author praised the individualized homeopathic treatment, the in-
tention-to-treat analysis with last value carried forward in those lost to
follow-up and the stringent denition of “cure”. The nding of equiv-
alent results in patients treated with homeopathy, compared to those
treated with antibiotics is an important rst step in order to assess the
effectiveness of either clinical approach to this disease.
In summary, equivalence trials of individualized homeopathy are
few, but together show that homeopathic treatments may have posi-
tive outcomes, similar or even better than conventional approach.
Equivalence Trials of Ailment Specic Formulations
One of the earliest of these was the study by Gassinger and co-
workers in 1981 [42]. In a controlled clinical trial, patients suffering
from the common cold were randomly assigned to treatment with
acetylsalicylic acid or with the medicine Eupatorium perfoliatum in
a low dilution. The efcacy of the drugs was assessed on days 1, 4
and 10 of the infection through symptom check lists and physical ex-
aminations. Neither the subjective symptoms, nor body temperature,
nor the laboratory data differed signicantly between the two groups,
leading the authors to conclude that the homeopathic treatment was
as effective as the allopathic treatment. Similar results to those of the
above study were also obtained by Maiwald and coworkers in 1988
in a simple blind randomized trial on a group of soldiers in the Ger-
man Army suffering from the common cold, and treated with ace-
tylsali-cylic acid or with a complex homeopathic preparation called
Grippheel (made from low potencies of Aconitum, Bryonia, Lachesis,
Eupatorium perfoliatum and Phosphorus). A comparison between
changes in clinical status and subjective disorders on days 4 and 10,
and between the length of time taken off work for the two groups, re-
vealed no signicant differences, leading the researchers to conclude
that the two therapeutic approaches are equi-effective. The same ho-
meopathic complex was evaluated in a prospective, observational
cohort study on patients suffering from mild viral infections of the
upper respiratory tract, with encouraging results, showing an equiva-
lent effectiveness of homeopathy and conventional medications [52].
An open, multicentre, prospective, active-controlled cohort study
was carried out on the homeopathic complex Euphorbium compos-
itum (nasal spray), whose effectiveness and tolerability were com-
pared with the reference allopathic drug xylometazoline [53]. The for-
mulation contains Euphorbium 4D, Pulsatilla 2D, Luffa operculata
2D, Mercurius bijodatus 8D, Mucosa nasalis suis 8D, Hepar sulfuris
10D, Argentum nitricum 10D, Sinusitis-Nosode 13D. Clinically rele-
vant reductions in the intensities of disease-specic symptoms were
observed in both groups. Non-inferiority of the homeopathic complex
medicine to xylometazoline could be shown for all the studied vari-
ables. Tolerability was good with both therapies.
A different complex that has been used in these kinds of respira-
tory complaints is Engystol-N (made of Vincetoxicum 6D, 10D and
30D, Sulfur 4D and 10D). In a non-randomized, observational study
Schmiedel and Klein compared the effects of Engystol with those of
conventional therapies with antihistamines, antitussives, and nonste-
roidal antiinammatory drugs on upper respiratory symptoms of the
common cold, over a treatment period of two weeks [57]. The effects
of treatment were evaluated in the variables of fatigue, sensation of
illness, chill/tremor, aching joints, overall severity of illness, sum of
all clinical variables, temperature and time to symptomatic improve-
ment. Both treatment regimens provided signicant symptomatic re-
lief, and signicantly more patients (p < 0.05) using Engystol-based
therapy reported improvement within 3 days (77.1% vs 61.7% for the
control group). Investigating the possible action mechanism, various
authors reported in vitro studies of this homeopathic complex that
showed antiviral and immunostimulating effects [93-96].
A prospective, multicenter, randomized, open, clinical trial carried
out in Russia analyzed a single homeopathic complex, called Cal-
Suli-4-02, on prevention of URTI in children [76]. CalSuli-4-02 is a
complex homeopathic medicinal product containing four active in-
gredients: Calcium carbonicum Hahnemanni 6D, Calcium uoratum
6D, Calcium phosphoricum 6D and Sulfur jodatum 12D. The Russian
regulatory authorities requested a comparison of the effectiveness and
safety of CalSuli-4-02 tablets with a comparable homeopathic prod-
uct, already marketed in Russia, for the prevention of URTIs (Genti-
ana 1D, Aconitum 6D, Bryonia 6D, Ferrum phosphoricum 12D, and
Acidum sar-colacticum 12D). It showed that both complexes deter-
mined a similar reduction of URTIs, with higher treatment satisfac-
tion and tolerability in the group treated with CalSuli-4-02.
In 2018, a prospective observational study was conducted with
the aim of understanding the choice of Pharmacists in prescribing
cough syrups in 414 children [82]. Regarding the two homeopathic
syrups, the results - were recorded by pharmacists were as follows:
Drosetux” (Drosera 3C, Arni-ca montana 3C, Belladonna 3C, Cina
3C, Coccus cacti 3C, Corallium rubrum 3C, Cuprum metalli-cum 3C,
Ferrum phosphoricum 3C, Ipeca 3C, Solidago virga aurea 1C) or
Stodal (Antimonium tartaricum 6C, Bryonia 3C, Coccus cacti 3C,
Drosera MT, Ipeca 3C, Myocardium 6C, Pulsatilla 6C, Rumex cris-
pus 6C, Spongia tosta 3C, Sticta pulmonaria 3C, Tolu syrup, Polygala
syrup) . Authors assessed the evolution of the cough, tolerance and
satisfaction with the treatment, administering a questionnaire after 5
days of treatment. Two-third of parents showed satisfaction; both with
homeopathic or allopathic medicines, and adverse effects were higher
in children treated with allopathic drugs. Based on these observations,
the authors suggested that homeopathy may have a positive role to
play in the treatment of cough in children [82]. A quantitative com-
parison between the two different syrups used in the study was not
In summary, equivalence trials of ailment-specic homeopathic
formulations show encouraging results that together with randomized
studies suggest the effectiveness of these medicines.
Observational Studies of Individualized Homeopathy
The purpose of the observational study of Frei and Thurneysen
was to nd out how many children with AOM are relieved of pain
with individualized homeopathic treatment [49]. A group of chil-
dren with this condition rst received an individualized homeopathic
Citation: Bellavite P, Marzotto M, Andreoli B (2019) Homeopathic Treatments of Upper Respiratory and Otorhinolaryngologic Infections: A Review of Random-
ized and Observational Studies. J Altern Complement Integr Med 5: 068.
• Page 10 of 20 •
J Altern Complement Integr Med ISSN: 2470-7562, Open Access Journal
DOI: 10.24966/ACIM-7562/100068
Volume 5 Issue 2 • 100068
medicine in the pediatric ofce. If pain-reduction was not sufcient
after 6 h, a second (different) homeopathic medicine was given. After
a further 6 h, children who had not reached acceptable pain control
levels were started on antibiotics. The six more frequently prescribed
medicines were Pulsatilla, Belladonna, Sulphur, Phosphorus, Calci-
um carbonicum, Lycopodium. Acceptable pain control was achieved
in 39% of the patients after 6 h and 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.
A multi-centre, observational, prospective study evaluated the
therapeutic usefulness of homeopathic medicine in the management
of chronic sinusitis [67]. As a secondary objective, it also assessed the
effect of the same medicines on change in the radiological appearance
of inammatory signs. It was conducted at Institutes and Units of the
Central Council for Research in Homoeopathy, India and patients
were recruited between October 2005 and March 2010. Included pa-
tients totaled 628, aged between 10 and 60 years, of both sexes, with
positive ndings of sinusitis in X-rays, who were able to stop all other
treatments for at least 2 weeks before enrollment. Patients were se-
lected from eight centers and resided within reasonable travelling dis-
tance from the study site. The homeopathic prescription was classical-
ly based on repertorization and Materia Medica and started with 30C
potency, in a single dose (four globules daily) followed by placebo
(four pills of unmediated globules, daily). Follow up was weekly for
the rst month, fortnightly for the next two months and monthly for
the remaining period, until six months. 39 patients dropped out from
the study after 3 months of treatment. The study revealed highly sig-
nicant improvement in symptoms and X-ray appearances between
baseline and end of treatment in patients with CS, for which home-
opathy maybe effective. Among the rst 17 medicines ranking rst
or second grade in the rubric “inamma-24 tion, chronic, sinusitis”,
Silicea, Calcarea carbonica, Lycopodium, Phosphorus, Kali iodatum
were found to be most useful, having marked improvement.
Witt and coworkers evaluated homeopathic treatment of sinusitis
in a large prospective multi-centre observational study population.
Most frequently prescribed medicines were Sepia, Pulsatilla, Lyco-
podium, Phosphorus, Carcinosinum, Nux vomica, Sulphur, Natrium
muriaticum, Staphisagria, Silicea [62]. Successive patients present-
ing for homeopathic treatment were followed up for 2 years, and com-
plaint severity, health-related quality of life, and medication use were
regularly recorded. There were signicant improvements in com-
plaint severity and in quality of life scores at 3, 12, and 24 months, but
the observed improvements were still present in the 8-year follow-up.
Due to the observational nature of the study, the authors correctly
conclude that the observed results may be due to treatment but the
extent to which the clinical improvement may be due to the life-style
regulation and placebo or context effects needs clarication in future
explanatory studies.
An observational study of the individualized homoeopathic treat-
ment of recurrent upper respiratory tract infections in children below
the age of 5 was carried out at a private Homoeopathic Medical Col-
lege [63]. The number of attacks of URTI during the 6-month period
preceding the date of starting homoeopathic treatment (Control val-
ue), and during the 6-month period following the start of treatment
(Treatment value) were compared. The results of the study indicate
statistically signicant differences (p < 0.001) between the two data
sets in favor of the homeopathically treated cases.
In summary, the reported observational studies of individualized
homeopathy are 3 and 5 for URTI and otorhnolaryngological infec-
tions respectively. Results are mainly positive but, due to the study
design, no conclusions can be drawn about efcacy.
Observational Studies of Ailment-Specic Formulations
One of the major problems of URTI treatments, i.e., the decision
of whether or not to use antibiotics, was the object of an observational
study carried out in Italy [73]. The aim of this prospective, observa-
tional study was to investigate the effect of an homeopathic syrup,
or of the homeopathic syrup plus antibiotic, in the treatment of acute
cough caused by non-complicated upper respiratory tract infections
in children. It was conducted on 85 children, treated for 7 days. The
syrup used was “Stodal”, composed of Anemone pulsatilla 6 C, Ru-
mex crispus 6C, Bryonia dioica 3C, Ipecacuanha 3C, Spongia tosta
3C, Sticta pulmonaria 3C, Antimonium tartaricum 6C, Myocarde 6
C, Coccus cacti 3C, Drosera MT. Both groups showed a signicant
reduction in symptoms, but additional antibiotic prescription was re-
lated to more adverse side effects than the homeopathic syrup alone.
The effectiveness of homeopathy in acute tonsillitis was evalu-
ated in an open trial [46]. A xed combination of low dilutions of
three plant substances (Phytolacca americana, Guajacum ofci-nale,
Capsicum annuum) was used in patients with this condition and no
antibiotics were administered. According to the Materia Medica, this
homeopathic complex medicine should be characterized by immuno-
modulatory, analgesic, and anti-inammatory properties. A decrease
in the objective and subjective symptoms of acute tonsillitis symp-
toms was observed as early as 2.5 days after starting treatment; no
serious adverse side effects were reported. Similar results were then
reported by another observational study, that tested the same plant
combinations in 48 patients with symptoms of acute tonsillitis, more
than half of whom experienced alleviation of the principal symptom
(moderate or severe difculty in swallowing), within the rst 5 days
of treatment [48].
The efcacy and safety of a xed-combination homeopathic medi-
cation (Sinusitis PMD) consisting of Lobaria pulmonaria, Luffa oper-
culata, and Potassium dichromate were investigated in an open-label
practice-based study of patients with acute sinusitis [47]. Most pa-
tients received only the test medication and no antibiotics. After a
mean of 4 days of treatment, secretolysis had increased signicantly
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 the treatment, 81.5%
of patients described themselves as symptom free or signicantly im-
proved. Ad-verse drug-related side effects were not reported.
A non-interventional study, conducted to study the safety and ef-
fectiveness of a homeopathic complex (Contramutan N Saft) was car-
ried out on 1,050 patients of different ages, affected by the common
cold and treated for 8 days [72]. The used preparation is composed of
low doses (4.5 mg/100 ml) of mother tinctures of Echinacea angus-
tifolia and Eupatorium perfoliatum, plus 9 mg of Aconitum napellus
4D and Belladonna 4D. It assessed the safety, compliance and possi-
ble inuence on symptoms, in patients suffering from acute infections
of the upper airways (u-like infection and inammatory disorders
of the nose and throat). Visits were performed by 64 practices head-
ed by general practitioners and pediatricians, with practical experi-
ence in treatments with complementary medicines and homeopathy.
Citation: Bellavite P, Marzotto M, Andreoli B (2019) Homeopathic Treatments of Upper Respiratory and Otorhinolaryngologic Infections: A Review of Random-
ized and Observational Studies. J Altern Complement Integr Med 5: 068.
• Page 11 of 20 •
J Altern Complement Integr Med ISSN: 2470-7562, Open Access Journal
DOI: 10.24966/ACIM-7562/100068
Volume 5 Issue 2 • 100068
The study was organized in two visits, one at the start and one the end
of the study, and then additional phone contacts were possible. En-
rolled patients were older than 1 year and suffering from symptoms of
an acute catarrhal disease of the respiratory tract. They were divided
into three groups by age. Results showed that - it was very well toler-
ated, with a high treatment satisfaction and effectiveness. The product
resulted as safe and effective in adults, as in children, with very rare
adverse reactions of mild to moderate intensity over a very short time.
The frequency of homeopathic aggravations was very low, just like
homeopathic “proving” symptoms [72].
A controlled, observational study is a retrospective analysis of the
role of homeopathy in the prevention of respiratory tract infections
(without specication if of upper of lower tract) [75]. It was conduct-
ed on 459 patients from a single setting, 248 treated with Oscillococ-
cinum (a high dilution of duck It was conducted on 459 patients from
a single setting, 248 treated with Oscillococcinum (a high dilution
of duck liver and heart extract) and 211 not treated. The rst group
showed a greater reduction of RTIs episodes after the treatment, but
did not specify which kind of RTIs were diagnosed in the observed
patients. The same drug had been previously tested with partially pos-
itive results in the treatment of inuenza [38,97,98].
In summary, the reported observational studies of ailment-specic
medicines are 5 and 4 for URTI and otorhnolaryngological infections
respectively. Results are mainly positive and are in agreement with
the results of randomized trials.
Components of the Medicines
Although several homeopathic medicines have been recently
studied in experimental and clinical settings, most components of the
mixed formulations have their justication only inside the traditional
experiences made by accidental exposure or by pathogenetic trials.
Table 2 reports a list of components frequently included in homeo-
pathic medicines for cough and upper respiratory diseases and that
have been used with positive results in the investigations reported in
this review. The main active ingredients of the medicines are known
and also their toxicological effects at high doses on the organism,
while their healing effects were presumed on the basis of the “similia”
principle [99]. And are reported in traditional Materia Medicas.
Name Taxonomic classication and
active ingredients
Traditional Materia Medica (minimum extract
from generalities) [41] Contained in medicine
Plant origin
Aconitum napellus Ranuncolaceae. Contains aconitine,
tyramine dopamine.
Fear, anxiety, restlessness, fright; complaints and
tension caused by exposure to dry, cold weather;
inammatory fevers, serous membranes affected
Individualized in equivalence trials
[45,45,89,90]. Component of homeopathic
formulation Grippheel [92], Contramutan N
Saft [72], and Inucid [74,78].
Belladonna (Atropa
belladonna, deadly
night shade)
One of the most poisonous
plants, contains tropane alka-
loids including atropine, scopol-
amine, and hyoscyamine, which
are used as anticholinergics.
These alkaloids can be very tox-
ic at high dose.
Acts upon nervous system, producing active
congestion, excitement; marked action on the
vascular system, skin and glands; associated with
hot, red skin, ushed face, glaring eyes, throbbing
carotids, excited mental state, hyperaesthesia of all
senses, dryness of mouth and throat with aversion
to water; traditionally indicated for scarlet fever
[100]. Toxicological properties reviewed in
Kwakye [101].
Individualized in equivalence trial
[45]. Individualized in observational study
[49]. Component of Tonzolyt [71], Hyland’s
Ear drops [64,68], Contramutan N Saft
[72], and Drosetux [82]. Intoxication with ho-
meopathic medicine described in a case [102].
Bryonia dioica
(or alba)
Cucurbitaceae. The major active
components are cucurbitacin
glucosides. The biological activities
of these compounds are associated
with biosynthesis of eicosanoids and
corticosteroids, which are important
mediators in the immune, endocrine
and nervous systems. Potential
adaptogen (stress protective)
[103,104]. Dihydrocucurbitacin
D inhibits macrophage nitric oxide
generation [105]. Antioxidant
activity [106].
Acts on serous membranes , aching in every mus-
cle; pain worse by motion, irritable; dry cough,
rheumatic pains and swellings; choriza, tough
mucus in larynx and trachea.
Component of homepathic formulation
Grippheel [92], Stodal [69,73,82], and Inucid
[74,78]. Phytotherapeutic use in chronic ob-
structive pulmonary disease [107]. Component
of immunostimulant formulation [108].
Capsicum annuum
A species of the plant genus Capsi-
cum (peppers) native to southern.
This species is the most common
and extensively cultivated of the
domesticated capsicums
Diminished vital heat, indolent person; affects
the mucous membranes, producing a sensation of
constriction; burning pains and general chilliness.
Individualized in equivalence trial [45]. Com-
ponent of homeopathic formulation [46,48]
and of ICX72 [65].
Matricaria chamomilla is an an-
nual plant of the composite fam-
ily Asteraceae. Active ingrediily
Asteraceae. Active ingredients
include terpene bisabolol, farnesene,
chamazulene and avonoids
Sensitive, irritable; oversensitiveness, night-
sweats; sensitive to cold air and cold things.
Individualized in randomized trial [51]. Com-
ponent of homeopathic formula Component of
homeopathic formulation Hyland’s Ear drops
[64,68]. Individualized in equivalence trial
Drosera rotundi-
Droseraceae. Contains glucides,
various acids, avonoid pig-
ments, proteases, naphthoqui-
Affects markedly the respiratory organs; gastric
irritation and profuse expectoration; spasmodic,
dry irritative cough, like whooping-cough, the
paroxysms following each other very rapidly.
Component of homeopathic formulation
Stodal [69,73,82], Monapax [81], and Dro-
setux [82].
Citation: Bellavite P, Marzotto M, Andreoli B (2019) Homeopathic Treatments of Upper Respiratory and Otorhinolaryngologic Infections: A Review of Random-
ized and Observational Studies. J Altern Complement Integr Med 5: 068.
• Page 12 of 20 •
J Altern Complement Integr Med ISSN: 2470-7562, Open Access Journal
DOI: 10.24966/ACIM-7562/100068
Volume 5 Issue 2 • 100068
Eupatorium perfo-
Known as common boneset or
just boneset, is a North American
perennial plant in the aster family.
Sesquiterpene lactones are signature
compounds of the large Eupatorium
genus and of the Asteraceae family
in general.
Relieves pain in bones, limbs and muscles that
accompanies some forms of febrile disease; acts
principally upon the gastro-hepatic organs and
bronchial mucous membrane.
Tested in equivalence trial [42]. Component
of homeopathic formulation Grippheel [92]
Contramutan N Saft [72] Inucid [74,78].
Rubiacee. Contains emetine,
cephaline psycotrine (alkaloid),
ipecacuanic acid (tannin), ipe-
cacuanine (eteroside)
Action is on the ramications of the pneumogas-
tric nerve, producing spasmodic irritation in chest
and stomach; persistent nausea and vomiting,
which form the chief guiding symptoms; warm,
moist weather.
Component of homeopathic formulation
Stodal [69,73,82], Inucid [74,78], Monapax
[81], and Drosetux [82].
Lycopodium clavatum
The most widespread species in the
genus Lycopodium in the clubmoss
family. Bioactive secondary
metabolites in clubmosses include
triterpenoids with acetylcholinester-
ase inhibitor activity isolated from
this species.
Ailments gradually developing, functional power
weakening, with failures of the digestive powers,
where the function of the liver is disturbed;
temperaments of lymphatic constitution, with
catarrhal tendencies; symptoms characteristically
run from right to left, acts especially on right
side of body, and are worse from about 4 to 8
p.m. Lacks vital heat; has poor circulation, cold
extremities. Sensitive to noise and odors.
Individualized in equivalence trials [45,66].
Individualized in observational studies
[49,62,67]. Component of homeopathic for-
mulation Hyland’s Ear drops [64,68].
Pulsatilla nigricans
Ranuncolaceae. Contains ane-
monine, roanemonine (alkaloids)
Especially for mild, gentle, yielding disposition;
sad, crying readily; weeps when talking; change-
able, contradictory; mucous membranes are all
affected; great sensitiveness.
Individualized in randomized trial [51].
Individualized in equivalence trials [45,66].
Individualized in observational studies
[49,62]. Component of homeopathic formula-
tion Euphorbium compositum [53], Hyland’s
Ear drops [64,68], Stodal [69,73,73,82], and
Cold‘n’ Cough for Kids [79].
Animal origin
Calcarea carbonica
Made from the middle layer of
shells. In chemical terms, Cal-
carea carbonica is impure calci-
um carbonate, CaCO
Chief action is centered in the vegetative sphere,
impaired nutrition being the keynote of its
action; increased perspiration, swelling of glands,
scrofulous and rachitic conditions; tickling cough,
eeting chest pains, nausea; gets out of breath
easily; great sensitiveness to cold.
Individualized in randomized trial [51]. Indi-
vidualized in observational studies [49,67].
Component of homeopathic formulation
Hyland’s Ear drops, [64,68] and CalSuli-4-02
Coccus cacti
Cocciniglia, insect (Hemiptera)
infesting cactus plants. The dried
bodies of the female are used for
making a tincture. Carminic Acid e
Spasmodic and whooping coughs, and catarrhal
conditions of the bladder; spasmodic pains in
kidneys, with visceral tenesmus; coryza, with
inamed fauces; accumulation of thick viscid
mucus, which is expectorated with great difculty;
tickling in larynx.
Component of homeopathic formulation
Stodal [69,73,82], Monapax [81], and Dro-
setux [82].
Mineral Origin
Calcarea carbonica
Made from the middle layer of
shells. In chemical terms, Calcarea
carbonica is impure calcium carbon-
ate, CaCO
Chief action is centered in the vegetative sphere,
impaired nutrition being the keynote of its
action; increased perspiration, swelling of glands,
scrofulous and rachitic conditions; tickling cough,
eeting chest pains, nausea; gets out of breath
easily; great sensitiveness to cold.
Individualized in randomized trial
[51]. Individualized in observational studies
[49,67]. Component of homeopathic formula-
tion Hyland’s Ear drops [64,68] and CalSu-
li-4-02 [76].
Ferrum phos-
phoricum Phospohate of iron
In the early stages of febrile conditions; the typical
subject is nervous, sensitive, anaemic; prostration
marked; susceptibility to chest troubles; bronchitis
of young children.
Component of homeopathic formulation
Sinfrontal [60] and Drosetux [82].
Hepar sulphuris
A burned combination the inner
layer of oyster shells (Calcarea
carbonica ) with owers of sul-
fur. It is also known as calcium
sulde. Hepar is the
Latin word for liver, as certain
compounds of sulfur had the color
of liver.
Lymphatic constitutions; unhealthy skin; great
sensitiveness to all impressions; special afnity
to the respiratory mucous membrane, producing
catarrhal inammation, profuse secretion; marked
tendency to suppuration; chilliness, hypersen-
sitiveness, feeling as if wind were blowing on
some part.
Component of Tonzolyt [71], Euphor-
bium compositum [53], Cold‘n’ Cough
for Kids [79], SilAltro-5-90 [80].
Kalium bichromi-
cum Potassium dichromate
Affects mucous membrane of stomach, bowels,
and airpassages; especially indicated for eshy,
fat, light complexioned persons subject to ca-
tarrhs; symptoms are worse in the morning; more
adapted to subacute rather than the violent acute
stage; mucous membranes everywhere are affect-
ed; catarrh of pharynx larynx, bronchi and nose.
Component of Tonzolyt [71], Sinusitis
PMD [47], SilAltro-5-90 [80].
In double-blind trial decreased tracheal
secretions in patients with chronic ob-
structive pulmonary disease [109].
Mercurius (biiodatus
or solubilis)
A liquid metallic chemical element
with the symbol ‘Hg’
The lymphatic system is especially affected;
traditionally indicated in the secondary stage
of syphilis; symptoms are worse at night, from
warmth of bed, from damp, cold, rainy weather;
complaints increase with the sweat and rest; all
associated with a great deal of weariness, pros-
tration, and trembling; sensitive to heat and cold;
breath, excretions and
body smell foul.
Individualized in equivalence trial [66].
Component of Tonzolyt [71], Euphorbium
compositum [53], SilAltro-5-90 [80], Sinfron-
tal [60].
Citation: Bellavite P, Marzotto M, Andreoli B (2019) Homeopathic Treatments of Upper Respiratory and Otorhinolaryngologic Infections: A Review of Random-
ized and Observational Studies. J Altern Complement Integr Med 5: 068.
• Page 13 of 20 •
J Altern Complement Integr Med ISSN: 2470-7562, Open Access Journal
DOI: 10.24966/ACIM-7562/100068
Volume 5 Issue 2 • 100068
We have taken 40 original clinical studies on URTI and othori-
nologic complaints from PubMed. The overview of the literature in
the considered eld shows that there are several promising studies
tending to support a clinically demonstrable activity of homeopathic
medicines. However, the body of randomized studies within the var-
ious elds is small, and “hard” proofs of efcacy, particularly when
considering single drugs or single clinical approaches, remains frag-
mentary. Though the number of papers published in peer-reviewed
journals is increasing, many homeopathic clinical studies are still
characterized by low standards of methodology a problem which
is, however, equally common in the conventional medical literature
The problems of measuring the quality, the model validity and the
risk of bias of the literature on homeopathic treatments are consid-
erable. A systematic review of the homeopathy RCT literature in 24
different medical conditions by Mathie et al found 32 eligible trials,
12 of which were classed ‘uncertain risk of bias’, while 20 trials were
classed ‘high risk of bias’ [111]. Further reviews found signicant
inadequacies, with the majority of studies demonstrating uncertain or
high risk of bias. Of the 26 RCTs of non-individualized homeopathy
that were judged ‘not at high risk of bias’, only nine have been rat-
ed ‘acceptable model validity’ [112-114]. Observational studies have
even higher “intrinsic” risk of bias due to design, even if properly
done and with high number of patients included. A consensus about
the quality criteria of observational studies in homeopathy has still to
be reached.
The papers reported in this review are highly heterogeneous, in
terms of the investigated disease conditions, the tested drugs, and
their experimental designs. A meta-analysis was beyond the scope
and style of the current overview and we adopted a narrative ap-
proach, using a semi-quantitative evaluation, where multiple studies
on the same homeopathic approach for the same group of conditions
are available (Table 3). In summary, the reported literature shows a
positive evidence of homeopathic treatments in URTI (with the ex-
ception of individualized prescription, where the evidence is more
conicting) and otorynolaryngologic infections, especially with the
use of ailment specic formulations. It is probable that the greatest
number of studies done with homeopathic formulas with respect to in-
dividualized homeopathy reects technical motivations (easier study
of a precise drug compared to the individualized approach) and com-
mercial ones.
Table 2: Homeopathic medicines for the treatment of patients with symptoms of URTIs and othorhinolaryngologic infections. Only the medicines used in a minimum of two
scientic papers described in the review are reported.
Natrum muriaticum
Sea salt containing NaCl, potassium
chloride, magnesium chloride,
calcium, aluminum and
other minerals mucous membranes.
mucous membranes.
Symptoms of salt retention, and oedemas; remedy
for certain forms of intermittent fever, anaemia,
leukocytosis, many disturbances of the alimentary
tract and skin; great debility; most weakness
felt in the morning in bed; great liability to take
cold; dry
Individualized in observational study [62].
Component of homeopathic formulation
Cold‘n’ Cough for Kids [79].
Chemical element with symbol
P and atomic number 15. Ele-
mental phosphorus exists in two
major forms, white phosphorus
and red phosphorus. It is highly
ammable and pyrophoric (self-
igniting) upon contact with air.
Irritates, inames and degenerates mucous mem-
branes; causes yellow atrophy of the liver and sub-
acute hepatitis; tall, slender persons, narrow chest-
ed, with thin, transparent skin; nervous debility,
emaciation, amative tendencies; susceptibility to
external impressions, to light, sound, odors, touch,
electrical changes; inammation of the respiratory
Individualized in observational studies
[49,62,67]. Component of Cold‘n’ Cough for
Kids [79], Grippheel [92], Inucid [74,78].
Silica is a mineral and is pre-
pared from silicon dioxide found
in int, quartz, sandstone, and
many other common rocks
Increased susceptibility to nervous stimuli and ex-
aggerated reexes; diseases of bones, caries and
necrosis; stimulates the organism to re-absorb -
brotic conditions and scar-tissue; rachitic children;
suppurative processes; silica patient is cold, chilly,
wants plenty warm clothing, worse in winter.
Individualized in equivalence trials [45,66].
Individualized in observational studies
[62,67]. Component of SilAltro-5-90 [80].
Mineral with atomic number 16.
Sulfur is often referred to as
brimstone or owers of sulfur
Elective afnity for the skin, where it produces
heat and burning, with itching; made worse by
heat of bed; dislike of water, dry and hard hair and
skin, red orices; aversion to being washed; arous-
es the reactionary powers of the organism.
Elective afnity for the skin, where it produces
heat and burning, with itching; made worse
by heat of bed; dislike of water, dry and hard
hair and skin, red orices; aversion to being
washed; arouses the Individualized in equiv-
alence trial [66]. Component of homeopathic
formulation Engystol-N [57], Hyland’s Ear
drops, [64,68] Inucid [74,78], Cold‘n’ Cough
for Kids [79].
Citation: Bellavite P, Marzotto M, Andreoli B (2019) Homeopathic Treatments of Upper Respiratory and Otorhinolaryngologic Infections: A Review of Random-
ized and Observational Studies. J Altern Complement Integr Med 5: 068.
• Page 14 of 20 •
J Altern Complement Integr Med ISSN: 2470-7562, Open Access Journal
DOI: 10.24966/ACIM-7562/100068
Volume 5 Issue 2 • 100068
According to “Natural Medicines”, an authoritative resource for
complementary alternative and integrative therapies, a treatment can
be rated as “Likely effective” where the evidence is from multiple
(2+) RCT, without valid evidence to the contrary, or as “Possibly ef-
fective” where the evidence is from one or more RCT or two or more
population based or epidemiological studies and valid positive evi-
dence outweighs contrary evidence. Following these criteria, the ail-
ment-specic formulations in Table 3 are tentatively rated as “Likely
effective”, while the individualized treatment of otorynolaryngolog-
ical infections is rated as “possibly effective”. Despite the uncertain-
ties about the quality of the studies, the amount of research published
may be sufcient to refute any judgment claiming that homeopathy is
not effective in these diseases.
A recent review selected double-blind, Randomized Controlled
Trials (RCTs) or double-blind cluster-RCTs comparing oral home-
opathy medicinal products with identical placebo or self selected
conventional treatments to prevent or treat ARTIs (acute respiratory
tract infections) in children aged 0 to 16 years [115]. Authors included
only 8 papers with very different methods and drugs and made their
evaluation on “meta-analysis” of only two prevention and two treat-
ment trials. Due to the heterogeneity of methods and outcomes, this
review concluded that “pooling of two prevention and two treatment
studies did not show any benet of homeopathic medicinal products
compared to placebo in acute respiratory tract infections recurrence
or cure rates in children”. Therefore, the negative conclusion could be
reached by excluding the vast majority of results reported in the liter-
ature and even in the 8 papers included in the review itself, by analyz-
ing separately prevention and treatment outcomes and by “pooling”
only two papers in each category. This procedure of “eliminating”
papers that do not t in the scheme of analysis recalls the meta-analy-
sis of Shang where to conclude that homeopathy lacks clinical effect,
more than 90% of the available clinical trials had to be disregard-
ed [116]. Another drawback of excluding a large number of studies
is that the composition of the nally analyzed mix of conditions
becomes very important to the conclusion. Here, one must remember
that the overall conclusion made in meta-analyses relates to the over-
all efcacy of a heterogeneous group of treatments for a heteroge-
neous group of diseases. Also for this reason, we have given up trying
to obtain “certain” conclusions as to the drug efcacy through a me-
ta-analysis and, to provide a wider and more realistic perspective into
the current state of play, we thus described all the PubMed-referenced
literature, including also observational studies, studies made on adult
patients. Compared with the cited review, we excluded the 2016 study
of Siqueira, since it was a trial on inuenza [115,117].
Besides conventional randomized placebo-controlled trials, ob-
servational studies allow the use of individualized patient treatment,
generally without the use of placebo or control group. By this way,
they can have less restricted inclusion criteria, to mimic the “real life”
setting of homeopathic practice. A pragmatic framework evaluat-
ing long-term effects in different settings, in conjunction with other
healthcare services was reported in a review on homeopathic treat-
ment of otitis media [118]. More recently, a review considered the
studies conducted after 1994 in URTIs and included 9 Randomized
Controlled Trials (RCTs) and 8 observational/cohort studies [119].
Results for homeopathy treatment were positive overall, with faster
resolution, reduced use of antibiotics and possible prophylactic and
longer-term benets. Authors concluded that at least an equivalence
exists between homeopathic and allopathic treatments and suggested
that homeopathy may represent a possible alternative in the treatment
for uncomplicated URTIs, having regard to the growing problem of
the antibiotic resistance.
Table 3: Summary of homeopathic treatments classied for specic indications and outcomes. Randomized studies are reported in bold characters.
aTo summarize the effectiveness, we used the criteria of Natural Medicines ( (see
text). bIt employed a method of uncertain validity, where one of 3 pre-selected drugs was chosen by parents; cAccording to the criteria mentholated in Methods, the effectiveness of
this approach is “possibly uneffective”, but it can be judged as “possibly effective” by excluding the paper of Steinsbekk 2005 for the reasons described in the text and in the previous
note [b]; dAdjunctive homeopathic therapy to conventional therapy [54].
Ailment Treatment type
Results Effectivenes
Positive evidence (vs. no
therapy or vs. placebo)
Positive evidence (equivalence
with conventional care)
Uncertain or
border line Negative evidence
Upper respiratory
tract infections
(ICD-10-CM diag-
nosis code J06)
Individualized pre-
scription Ramchandani 2010 [63]
Steinsbekk 2005 [55]
Riley 2001 [50]
Haidvogl 2007 [59]
de Lange de
Klerk 1994 [44] Steinsbekk 2005
[54] Uncertain
Ailment specic
Zanasi 2014 [69]
Thinesse-Mallwitz 2015 [74]
Jong 2016 [76]
Van Haselen 2016 [78] [4]
Voss 2018 [81] Beghi 2016 [75]
Allaert 2018 [82]
Rabe 2004 [52]
Grimaldi-Bensouda 2014 [70]
Zanasi 2015 [73]
Likely effective
logical infections
Jacobs 2001 [51]
Frei 2001 [49]
Witt 2009 [62]
Nayak 2012 [67]
Sinha 2012 [66]
Fiese 1997 [45]
Trichard 2005 [56]
Possibly effective
Ailments specic
Zabolotnyi 2007 [60]
Taylor 2011 [64]
Bernstein 2011 [65]
Taylor 2014 [68]
Malapane 2014[71]
Jacobs 2016 [79]
Palm 2017 [80] [4]
Michalsen 2015 [72]
Wiesenauer 1998 [46]
Rau 2000 [48]
Gassinger 1981 [42]
Maiwald 1988 [92]
Ammerschlager 2005 [53]
Schmiedel 2006 [57]
Adler 1999 [47] Pedrero-Escalas 2016 [77]
Likely effective
Citation: Bellavite P, Marzotto M, Andreoli B (2019) Homeopathic Treatments of Upper Respiratory and Otorhinolaryngologic Infections: A Review of Random-
ized and Observational Studies. J Altern Complement Integr Med 5: 068.
• Page 15 of 20 •
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DOI: 10.24966/ACIM-7562/100068
Volume 5 Issue 2 • 100068
Literature on homeopathy for otitis is relatively small; neverthe-
less this literature overview suggests that in many instances it is as
effective as a standard treatment. The suggestion is that management
of otitis media should begin with patient observation. At this time,
homeopathic medicines may help decrease pain and lead to faster
resolution. Key factors in implementing a “wait and watch” strategy
were (a) a method to classify AOM severity; (b) parent education; (c)
management of AOM symptoms; (d) access to follow-up care; and
(e) use of an effective antibiotic regimen, when needed. When these
caveats are observed, “wait and watch” may be an acceptable alterna-
tive to immediate antibiotics for some children with non-severe AOM
[24]. More randomized controlled studies are expected to assess the
efcacy and safety of specic formulations. The research needs to be
reproduced and its conclusions need to be conrmed, before being
used as indications in clinical practice for the general population. It
is important to remember and underline once again that “absence of
evidence” is not synonymous with “evidence of absence”.
There is sharp controversy concerning the “plausibility” of home-
opathy [120-123]. Though we do not have space here to discuss the
purported mechanisms of homeopathic effects, it is worth mentioning
that even basic in vitro experimental studies provide evidence that
the effects of homeopathic solutions differ from pure diluting solvent
[86,124-129]. The results of basic research experiments may invigo-
rate new clinical trials that investigate complementary treatments for
infectious diseases [130]. Some homeopathic medicines showed di-
rect effects on the immune system cells [131-136], or exerted antiviral
action [93,136-138].
The limitation of this study is the lack of a detailed quality analysis
of each included study, because our object was essentially descriptive
and not to draw quantitative conclusions, or clinical recommenda-
tions. Although a publication bias cannot be excluded, we assumed
that publications in peer-reviewed journal and reviewed by PubMed
had sufcient quality for inclusion, since the papers have been ex-
amined by experts in their sector before being published. Neither
have we attempted any meta-analysis of clinical trials, since there is
a marked heterogeneity between studies, either in the different meth-
ods of homeopathic treatment (e.g., Individualized or complex, worth
different drugs), or in the models of study, that in homeopathy are
still under scrutiny [139]. Others have shown that pooling data from
heterogeneous clinical trials in homeopathy and using funnel plot to
analyze papers with largely different sample sizes, as done in a fa-
mous meta-analysis on homeopathy, may lead to awed conclusions
Another limitation of our present study concerns the tentative
conclusions made about ailment specic products. While the evalua-
tion of the literature provided a basic evidence of a likely therapeutic
effect in URTI and othorhinolaryngologic ailments, the existence of
many different homeopathic products with different composition pre-
cludes the identication of the substance that is actually responsible
for the purported curative effect. What emerges from this overview
is an efcacy/effectiveness paradox, similar to that found in several
other areas of complementary medicine research, with weak evidence
in favor of homeopathy when studies are done in randomized and
double-blind conditions, yet documented effectiveness in equivalence
studies comparing homeopathy and conventional medicine, and doc-
umented usefulness in general practice through observational studies:
the therapy seems useful when applied in open practice and produces
substantive effects, even in patients with chronic diseases [38]. Most
of the studies reviewed here suggest that homeopathic medicines in
high dilutions, prescribed by trained professionals, are safe and un-
likely to provoke severe adverse reactions. This leads us to conclude
that, even though most decisions about treatments still rest in the
hands of the individual judgments of clinicians and patients, addition-
al clinical research, both experimental and observational, including
studies using different approaches, is necessary for further developing
the base of evidence for homeopathy. It would also be interesting to
compare the effectiveness of different forms of homeopathy for the
same condition. However the small sizes of the studied populations
and the differences between them, have thus far not per-mitted any
reliable quantitative evaluation.
In this work we have described and classied the most important
homeopathic investigations in the elds considered and put forward
a semi-quantitative evaluation criterion, which allows evaluating the
whole set of results without discarding any work, as they did instead
previous meta-analyses. In a relatively small eld like homeopathy,
where scientic research is still in its infancy and there is no con-
sensus on the model validity of different approaches, we have the
advantage of including the contribution, albeit partial, of each publi-
cation of sufcient validity and therefore of having an overall view
of literature. In the light of the clinical ndings, the use of individu-
alized homeopathy or homeopathic medicines could be regarded as
a possible option in the elds reviewed in this work particularly in
the infections of upper airways, otitis and rhinopharyngitis provided
that the homeopathic diagnosis and prescription is correct and is inte-
grated with other possible effective treatments. However, much more
work is needed both to produce new evidence with ever more precise
and correct clinical research, and to rene the criteria for evaluating
the homeopathic literature ac-cording to parameters shared by the ho-
meopathic community.
Conict of Interest
The authors declare there is no conict of interest. The paper was
written without funding. Sponsors of previous and current research
carried out by the group at Verona University did not interfere with
the design of the study, collection, analysis or interpretation of data.
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... 2-022.7:578]-036. 11:615.015. 32-085.036.8 ...
... У всіх названих країнах Європи, кращих за світовим рейтингом національних служб охорони здоров'я, гомеопатія присутня як складова доказової медицини, що входить у структуру страхової медицини. Так, у Франції, що посідає перше місце в цьому рейтингу, гомеопатія входить у структуру страхової медицини, там не тільки застосовується гомеопатія вже понад 200 років, але й проводяться подвійні сліпі плацебо-контрольовані міжнародні багатоцентрові рандомізовані клінічні дослідження з ефективності й безпечності гомеопатичних лікарських засобів у практичній охороні здоров'я [11]. ...
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В данной обзорной статье речь идет о необходимости понимания основы эффективности и безопасности применения гомеопатических лекарственных препаратов при острых респираторных вирусных инфекциях (ОРВИ) с позиции доказательной медицины. Гомеопатические лекарственные препараты рассмотрены с точки зрения составляющей наномедицины с учетом открытий, сделанных в течение последних десятилетий в этой области знаний, а также с учетом того, что течение ОРВИ в основном проявляется функциональными нарушениями. Отмечена целесообразность использования отдельных компонентов гомеопатических лекарственных средств именно в низких/гомеопатических/наноконцентрациях с учетом их дозозависимого профиля безопасности. В качестве примера проанализированы препараты французского происхождения — Оциллококцинум, Коризалия, Гомеовокс и Стодаль. За многие десятилетия практического использования указанных препаратов наработана достаточно весомая научная база, существует ряд статей, опубликованных в различных странах мира, подтверждающих их эффективность и безопасность. Рассмотрены не только клинические исследования относительно вышеупомянутых препаратов, но также ­освещены вопросы механизма их действия на основе фармакодинамических свойств отдельных компонентов. Указана необходимость рассматривать любой лекарственный препарат, в том числе гомеопатический, как с позиции доказательной медицины, так и в более широком смысле, с учетом современного подхода к здравоохранению на основе ценности. С учетом проанализированной информации сделан вывод, что вышеупомянутые препараты — Оциллококцинум, Коризалия, Гомеовокс, Стодаль — отвечают этим требованиям и должны быть более широко внедрены в клиническую практику.
From December 2019, a new pandemic named Coronavirus Disease 2019 (COVID-2019) has become a key topic of discussion across the world. The reason behind this discussion is the rapid increase in human death due to COVID-19 which has stunned the world. The pathogen of COVID-19 is a novel coronavirus called Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) which is similar to SARS CoV. SARS-CoV-2 infects mainly the respiratory system which causes the death because there is no effective vaccines or therapeutics against COVID-19. Homoeopathic drugs like Lachesis and Gripp Heel may play an effective role to cure corona patients.
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Please note that the journal name is: “Journal of Alternative, Complementary and Integrative Medicine”. Introduction Homeopathy is a therapeutic natural medical alternative that is widely and increasing-ly being used, even for pediatric patients. Given this trend, it is essential that clinicians have the re-sources to advise their patients as to the potential benefits and harms of this complementary therapy. The aim of this work is to describe the available literature cited in PubMed concerning the ho-meopathic treatments on human subjects (both children and adult) for common upper respiratory tract infections (URTI), otitis, rhinitis, sinusitis, rhinosinusitis, pharyngitis and tonsillitis. Methods The PubMed search made use of the keywords “homeopathy” or “homeopathic”, and the names of the indicated diseases. The report covers all forms of homeopathic therapy, namely: a) classical individualized homeopathy, b) ailment-specific medicines and complexes. In order to take into account the whole mass of literature, the evidence of the clinical effectiveness is summarized according to semi-quantitative criteria, based on the number of randomized and non-randomized papers published in each group of ailments. The medicines used in the various studies are classified and described. Results A total of 40 clinical studies, published until the end of 2018, which assess the effective-ness of the homeopathic treatment in one of the abovementioned conditions are reported and classi-fied. The studies are randomized or equivalence studies with control group (n=21), non randomized or observational (n=19) and concern different clinical approaches, namely individualized using high homeopathic dilutions or non-individualized using complex drug formulations. Studies have re-vealed mixed results, suggesting that some homeopathic formulations may have significant effects in URTI and otorhinolaryngological infections. Several studies have demonstrated benefits to pa-tients’ quality of life and symptom scoring, or equivalence with the conventional medical approach. Scarcity of data and uncertainty still exists in literature on the effectiveness of individualized ap-proach in URTIs. 21 different medicines were used in a minimum of two published reports. Conclusion Homeopathic formulations in upper respiratory tract and otorhinolaryngological infec-tions are likely effective and the individualized approach in non severe otitis is possibly effective. Homeopathic treatments may help when use of antibiotics is not indicated. Due to the heterogeneity of approaches and of drugs used, additional studies will be required to evaluate the possible integra-tion of homeopathy into the standard of care for the treatment of respiratory and otorhinolaryngo-logic ailments.
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Inappropriate antibiotic use is a key factor in the emergence of antibiotic resistance. The majority of antibiotics are prescribed in primary care, where upper respiratory tract infection (URTI) is a common presentation. Inappropriate antibiotic prescribing in URTI is common globally and has increased markedly in developing and transitional countries. Antibiotic stewardship is crucial to prevent the emergence and spread of resistant microbes. This project aimed to reduce inappropriate antibiotic prescribing in URTI in a non-governmental organisation’s primary care outreach clinics in Kolkata, India, from 62.6% to 30% over 4 months. A multifaceted intervention to reduce inappropriate antibiotic use in non-specific URTI was implemented. This consisted of a repeated process of audit and feedback, interactive training sessions, one-to-one case-based discussion, antibiotic guideline development and coding updates. The primary outcome measure was antibiotic prescribing rates. A baseline audit of all patients presenting with non-specific URTI over 8 weeks in November and December 2016 (n=222) found that 62.6% were prescribed antibiotics. Postintervention audit over 4 weeks in April 2017 (n=69) showed a marked reduction in antibiotic prescribing to 7.2%. An increase in documentation of examination findings was also observed, from 52.7% to 95.6%. This multifaceted intervention was successful at reducing inappropriate antibiotic prescribing, with sustained reductions demonstrated over the 4 months of the project. This suggests that approaches previously used in Europe can successfully be applied to different settings.
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Introduction: Adaptogens are natural compounds or plant extracts that increase adaptability and survival of organisms under stress. Adaptogens stimulate cellular and organismal defense systems by activating intracellular and extracellular signaling pathways and expression of stress-activated proteins and neuropeptides. The effects adaptogens on mediators of adaptive stress response and longevity signaling pathways have been reported, but their stress-protective mechanisms are still not fully understood. Aim of the study: The aim of this study was to identify key molecular mechanisms of adaptogenic plants traditionally used to treat stress and aging-related disorders, i.e., Rhodiola rosea, Eleutherococcus senticosus, Withania somnifera, Rhaponticum carthamoides, and Bryonia alba. Materials and methods: To investigate the underlying molecular mechanisms of adaptogens, we conducted RNA sequencing to profile gene expression alterations in T98G neuroglia cells upon treatment of adaptogens and analyzed the relevance of deregulated genes to adaptive stress-response signaling pathways using in silico pathway analysis software. Results and discussion: At least 88 of the 3516 genes regulated by adaptogens were closely associated with adaptive stress response and adaptive stress-response signaling pathways (ASRSPs), including neuronal signaling related to corticotropin-releasing hormone, cAMP-mediated, protein kinase A, and CREB; pathways related to signaling involving CXCR4, melatonin, nitric oxide synthase, GP6, Gαs, MAPK, neuroinflammation, neuropathic pain, opioids, renin–angiotensin, AMPK, calcium, and synapses; and pathways associated with dendritic cell maturation and G-coupled protein receptor–mediated nutrient sensing in enteroendocrine cells. All samples tested showed significant effects on the expression of genes encoding neurohormones CRH, GNRH, UCN, G-protein–coupled and other transmembrane receptors TLR9, PRLR, CHRNE, GP1BA, PLXNA4, a ligand-dependent nuclear receptor RORA, transmembrane channels, transcription regulators FOS, FOXO6, SCX, STAT5A, ZFPM2, ZNF396, ZNF467, protein kinases MAPK10, MAPK13, MERTK, FLT1, PRKCH, ROS1, TTN), phosphatases PTPRD, PTPRR, peptidases, metabolic enzymes, a chaperone (HSPA6), and other proteins, all of which modulate numerous life processes, playing key roles in several canonical pathways involved in defense response and regulation of homeostasis in organisms. It is for the first time we report that the molecular mechanism of actions of melatonin and plant adaptogens are alike, all adaptogens tested activated the melatonin signaling pathway by acting through two G-protein–coupled membrane receptors MT1 and MT2 and upregulation of the ligand-specific nuclear receptor RORA, which plays a role in intellectual disability, neurological disorders, retinopathy, hypertension, dyslipidemia, and cancer, which are common in aging. Furthermore, melatonin activated adaptive signaling pathways and upregulated expression of UCN, GNRH1, TLR9, GP1BA, PLXNA4, CHRM4, GPR19, VIPR2, RORA, STAT5A, ZFPM2, ZNF396, FLT1, MAPK10, MERTK, PRKCH, and TTN, which were commonly regulated by all adaptogens tested. We conclude that melatonin is an adaptation hormone playing an important role in regulation of homeostasis. Adaptogens presumably worked as eustressors (“stress-vaccines”) to activate the cellular adaptive system by inducing the expression of ASRSPs, which then reciprocally protected cells from damage caused by distress. Functional investigation by interactive pathways analysis demonstrated that adaptogens activated ASRSPs associated with stress-induced and aging-related disorders such as chronic inflammation, cardiovascular health, neurodegenerative cognitive impairment, metabolic disorders, and cancer. Conclusion: This study has elucidated the genome-wide effects of several adaptogenic herbal extracts in brain cells culture. These data highlight the consistent activation of ASRSPs by adaptogens in T98G neuroglia cells. The extracts affected many genes playing key roles in modulation of adaptive homeostasis, indicating their ability to modify gene expression to prevent stress-induced and aging-related disorders. Overall, this study provides a comprehensive look at the molecular mechanisms by which adaptogens exerts stress-protective effects.
Background. The effectiveness of a homeopathic syrup on cough has been demonstrated in an adult population in a previous double-blind randomized study. The present prospective observational study investigated children affected by wet acute cough caused by non-complicated URTIs, comparing those who received the homeopathic syrup versus those treated with the homeopathic syrup plus antibiotic. Objectives. The aims were: 1) to assess whether the addition of antibiotics to a symptomatic treatment had a role in reducing the severity and duration of acute cough in a pediatric population, as well as in improving cough resolution; 2) to verify the safety of the two treatments. Methods. Eighty-five children were enrolled in an open study: 46 children received homeopathic syrup alone for 10 days and 39 children received homeopathic syrup for 10 days plus oral antibiotic treatment (amoxicillin/clavulanate, clarithromycin, and erythromycin) for 7 days. To assess cough severity we used a subjective verbal category-descriptive (VCD) scale. Results. Cough VCD score was significantly (P < 0.001) reduced in both groups starting from the second day of treatment (−0.52 ± 0.66 in the homeopathic syrup group and −0.56 ± 0.55 in children receiving homeopathic syrup plus oral antibiotic treatment). No significant differences in cough severity or resolution were found between the two groups of children in any of the 28 days of the study. After the first week (day 8) cough was completely resolved in more than one-half of patients in both groups. Two children (4.3 %) reported adverse effects in the group treated with the homeopathic syrup alone, versus 9 children (23.1 %) in the group treated with the homeopathic syrup plus antibiotics (P = 0.020). Conclusions. Our data confirm that the homeopathic treatment in question has potential benefits for cough in children as well, and highlight the strong safety profile of this treatment. Additional antibiotic prescription was not associated with a greater cough reduction, and presented more adverse events than the homeopathic syrup alone.
Introduction This study focuses on randomised controlled trials (RCTs) of non-individualised homeopathic treatment (NIHT) in which the control (comparator) group was other than placebo (OTP). Objectives To determine the comparative effectiveness of NIHT on health-related outcomes in adults and children for any given condition that has been the subject of at least one OTP-controlled trial. For each study, to assess its risk of bias and to determine whether its study attitude was predominantly ‘pragmatic’ or ‘explanatory’. Methods Systematic review. For each eligible trial, published in the peer-reviewed literature up to the end of 2016, we assessed its risk of bias (internal validity) using the seven-domain Cochrane tool, and its relative pragmatic or explanatory attitude (external validity) using the 10-domain PRECIS tool. We grouped RCTs by whether these examined IHT as alternative treatment (study design 1a), adjunctively with another intervention (design 1b), or compared with no intervention (design 2). RCTs were sub-categorised as superiority trials or equivalence/non-inferiority trials. For each RCT, we designated a single ‘main outcome measure’ to use in meta-analysis: ‘effect size’ was reported as odds ratio (OR; values > 1 favouring homeopathy) or standardised mean difference (SMD; values < 0 favouring homeopathy). Results Seventeen RCTs, representing 15 different medical conditions, were eligible for study. Three of the trials were more pragmatic than explanatory, two were more explanatory than pragmatic, and 12 were equally pragmatic and explanatory. Fourteen trials were rated ‘high risk of bias’ overall; the other three trials were rated ‘uncertain risk of bias’ overall. Ten trials had data that were extractable for analysis. Significant heterogeneity undermined the planned meta-analyses or their meaningful interpretation. For the three equivalence or non-inferiority trials with extractable data, the small, non-significant, pooled effect size (SMD = 0.08; p = 0.46) was consistent with a conclusion that NIHT did not differ from treatment by a comparator (Ginkgo biloba or betahistine) for vertigo or (cromolyn sodium) for seasonal allergic rhinitis. Conclusions The current data preclude a decisive conclusion about the comparative effectiveness of NIHT. Generalisability of findings is restricted by the limited external validity identified overall. The highest intrinsic quality was observed in the equivalence and non-inferiority trials of NIHT.
Objectives The aim of the present study consisted in the isolation of flavonoids from the leaves of Bryonia alba L. and evaluation of their antioxidant activity and inhibition on peroxidase‐catalysed reactions. Methods Flavonoids were isolated by preparative HPLC‐DAD and their structures were elucidated by MS and NMR. Inhibitory effect was tested by the horseradish peroxidase and the myeloperoxidase assays. Cellular antioxidant assays consisted in testing the inhibitory activity on the reactive oxygen species released upon activation of neutrophils freshly isolated ex vivo from equine blood and of human monocytes‐derived macrophages in vitro. Whole organism toxicity was assessed on zebrafish larvae. Key findings Four flavonoids (lutonarin, saponarin, isoorientin and isovitexin) were isolated. The performed assays showed significant antioxidant activity and inhibition for the peroxidase‐catalysed reactions. Absence of cellular and zebrafish toxicity was confirmed. Conclusions Bryonia alba L. leaves are particularly interesting for their flavonoids content and showed significant inhibitory effect on peroxidase‐catalysed oxidation of substrates (Amplex Red and L012), as well as antioxidant/antiradical activity, proving that this species has a medicinal potential. Moreover, the present study highlights the absence of the toxicity of these leaves and offers though a novel perspective on the species, previously known as being toxic.
Introduction There are two critical pillars of homeopathy that contrast with the dominant scientific approach: the similitude principle and the potentization of serial dilutions. Three main hypotheses about the mechanisms of action are in discussion: nanobubbles-related hormesis; vehicle-related electric resonance; and quantum non-locality. Objectives The aim of this paper is to review and discuss some key points of such properties: the imprint of supramolecular structures based on the nanoparticle-allostatic, cross-adaptation-sensitization (NPCAS) model; the theory of non-molecular electromagnetic transfer of information, based on the coherent water domains model, and relying (like the NPCAS model) on the idea of local interactions; and the hypothesis of quantum entanglement, based on the concept of non-locality. Results and Discussion The nanoparticles hypothesis has been considered since 2010, after the demonstration of suspended metal nanoparticles even in very highly diluted remedies: their actual action on biological structures is still under scrutiny. The second hypothesis considers the idea of electric resonance mechanisms between living systems (including intracellular water) and homeopathic medicines: recent findings about potency-related physical properties corroborate it. Finally, quantum theory of ‘non-local’ phenomena inspires the idea of an ‘entanglement’ process among patient, practitioner and the remedy: that quantic phenomena could occur in supra-atomic structures remains speculative however. Conclusion Further studies are needed to ascertain whether and which of these hypotheses may be related to potential cellular effects of homeopathic preparations, such as organization of metabolic pathways or selective gene expression.
Background Homeopathy has been used to treat epidemic diseases since the time of Hahnemann, who used Belladonna to treat scarlet fever. Since then, several approaches using homeopathy for epidemic diseases have been proposed, including individualization, combination remedies, genus epidemicus, and isopathy. Methods The homeopathic research literature was searched to find examples of each of these approaches and to evaluate which were effective. Results There is good experimental evidence for each of these approaches. While individualization is the gold standard, it is impractical to use on a widespread basis. Combination remedies can be effective but must be based on the symptoms of a given epidemic in a specific location. Treatment with genus epidemicus can also be successful if based on data from many practitioners. Finally, isopathy shows promise and might be more readily accepted by mainstream medicine due to its similarity to vaccination. Conclusion Several different homeopathic methods can be used to treat epidemic diseases. The challenge for the future is to refine these approaches and to build on the knowledge base with additional rigorous trials. If and when conventional medicine runs out of options for treating epidemic diseases, homeopathy could be seen as an attractive alternative, but only if there is viable experimental evidence of its success.
Atropa belladonna, commonly known as belladonna or deadly nightshade, ranks among one of the most poisonous plants in Europe and other parts of the world. The plant contains tropane alkaloids, including atropine, scopolamine, and hyoscyamine, which are used as anticholinergics in Food and Drug Administration (FDA) approved drugs and homeopathic remedies. These alkaloids can be very toxic at high dose. The FDA has recently reported that Hyland's baby teething tablets contain inconsistent amounts of Atropa belladonna that may have adverse effects on the nervous system and cause death in children, thus recalled the product in 2017. A greater understanding of the neurotoxicity of Atropa belladonna and its modification of genetic polymorphisms in the nervous system is critical in order to develop better treatment strategies, therapies, regulations, education of at-risk populations, and a more cohesive paradigm for future research. This review offers an integrated view of the homeopathy and neurotoxicity of Atropa belladonna in children, adults and animal models, as well as its implications to neurological disorders. Particular attention is dedicated to the pharmaco/toxicodynamics, pharmaco/toxicokinetics, pathophysiology, epidemiological cases, and animal studies associated with the effects of Atropa belladonna on the nervous system. Additionally, we discuss the influence of active tropane alkaloids in Atropa belladonna and other similar plants on FDA-approved therapeutic drugs for treatment of neurological disorders.