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Systematic Review in Vitro Evidence for an Effect of High Homeopathic Potencies 2007

Systematic Review in Vitro Evidence for an Effect of High Homeopathic Potencies 2007

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Complementary Therapies in Medicine (2007)
, 128—138
in vitro
evidence for an effect of highhomeopathic potencies—–A systematic review of the literature
Claudia M. Witt
, Michael Bluth
, Henning Albrecht
,Thorolf E.R. Weißhuhn
, Stephan Baumgartner
, Stefan N. Willich
Institute for Social Medicine, Epidemiology and Health Economics, Charit´e University Medical Center,D-10098 Berlin, Germany 
Klinik f ¨ur Tumorbiologie, D-Freiburg/Br, Germany 
Karl and Veronica Carstens-Foundation, D-Essen, Germany 
Institute for Complementary Medicine (KIKOM), University of Bern, CH-Bern, Germany 
Available online 28 March 2007
Homeopathy;Potency;Dynamization;Basic research;Quality assessment;Quality score;Modified SAPEH;BEPEV;Cell-free systems;Non-cellular;Cultured cells;Basophiles;Neutrophiles;Lymphocytes;
In vitro
Systematic assessment of the
in vitro
research on high potency effects.
Publications of experiments were collected through databases, experts,previous reviews, citation tracking. Inclusion criteria: stepwise agitated dilutions<10
; cells or molecules from human or animal. Experiments were assessed withthe modified SAPEH score.
From 75 publications, 67 experiments (1/3 of them replications) were eval-uated. Nearly 3/4 of them found a high potency effect, and 2/3 of those 18 thatscored 6 points or more and controlled contamination. Nearly 3/4 of all replicationswere positive. Design and experimental models of the reviewed experiments wereinhomogenous, most were performed on basophiles.
Even experiments with a high methodological standard could demon-strate an effect of high potencies. No positive result was stable enough to bereproduced by all investigators. A general adoption of succussed controls, random-ization and blinding would strengthen the evidence of future experiments.© 2007 Elsevier Ltd. All rights reserved.
Corresponding author. Tel.: +49 30 450529011;fax: +49 30 450529902.
E-mail address:
Homeopathic remedies are prepared (‘potentized’or ‘dynamized’) in steps of alternately dilutingand succussing a homeopathic stock
(historicallyknown as ‘mother tincture’). After several steps,
0965-2299/$ — see front matter © 2007 Elsevier Ltd. All rights reserved.doi:10.1016/j.ctim.2007.01.011
In vitro research on high potencies 129the remedies reach calculatory dilutions beyondAvogadro’s number, implying a non-molecularaction of remedies with specific healing proper-ties. Research in this field arranges around threecore problems
:(1) What are the therapeuticeffects of homeopathic remedies? (2) What are thespecific characteristics of potencies? (3) Throughwhat mechanism(s) do they influence the organism?Relating to (1) and (3),
in vitro
research searchesfor effects of potentized remedies on molecularor cellular systems. Reducing complexity this wayallows a higher degree of standardization than clin-ical research, and may eventually provide modelsystems to reveal the mode of action of high dilu-tionsdevoidofpharmacologicallyactivemolecules.Previous reviews of the field have been eitherdescriptions of individual experiments without sys-tematic evaluation
,investigations of only theindependence of replications
,or do not presentdetails and rationales of their scoring procedure.
Other restrictions had been set on publicationslanguage
or research area,
so that a bothbroad and systematic assessment with transparentcriteria does not exist. In this evaluation we there-fore systematically assessed the
in vitro
researchon effects of high potencies of a stock preparationby using a score system. Additionally, we tried toidentify experimental models that provide repro-ducible results or promising approaches that shouldbe replicated.
Inclusion criteria and data sources
We searched for written publications of 
in vitro
investigations on high potencies.
In vitro
wasdefined as ‘concerning cellular or subcellular enti-ties in isolation from a living organism’. Thisincluded cells (also from cultures) or molecules,but not isolated organs. All systems had to beof human or animal origin. Pathological materialssuch as cancer cells or cells from allergic donatorswere accepted. Pretreatment before cell extrac-tion, such as intoxication or sensitization, wasallowed, but the application of homeopathic prepa-rations had to be
in vitro
only. Tested remedies hadto include high potencies that imply a calculatorydilution of at least 10
C12). Rem-edy mixtures (‘complex remedies’) were allowed.No other restrictions were imposed; all publicationlanguages were included.References from the Basic Research Databaseof the Karl and Veronica Carstens-Foundation,D-Essen,
were collected until December2005 by searching for hom¨oopathie+basicresearch+experimental+
in vitro
’ in each of thefollowing fields: immunology, toxicology, phar-macology, neurology, biochemistry. Medline
wassearched for publications of the years 1966 untilDecember 2005 using MeSH and full text termsin various spellings. Searched was for ‘home-opathycombined with each of the followingterms:
in vitro
’; ‘cell culture’; ‘tissue culture’;‘cells, cultured’; ‘granulocyte’; ‘lymphocyte’;‘macrophage’; ‘neutrophil’; ‘basophil’; ‘enzyme’;‘biomolecule’; ‘immunocompetent’. Amed
(Alliedand Alternative Medicine) was searched from 1985to December 2005 using the same search as inMedline. Previous reviews,
and all obtainedpublications were screened for further references.In addition, we asked experts for information.
Data extraction
Fromtheidentifiedreferences,thosetooshortforasensible scoring were excluded, among them wereall abstracts. From publications that were mostlyor fully identical or obviously referring to identi-cal experiments only the most detailed descriptionwas included. One author (MB) extracted data andscoredtheexperimentsexcepthisownpaper
thatwas scored by another author (SB) who did notparticipate in this work, the data were discussedwith a second author (CMW). For each experimentthe following data were extracted: publication,objective, technique, findings, substance tested,control or comparison, and solvent of potentizing,together with additional information of inter-est. All identified publications were classified bysystem: non-cellular systems (enzymes), or cel-lular systems of the categories cultured cells,erythrocytes, basophile granulocytes, neutrophilegranulocytes, and lymphocytes/mononuclear cells(including experiments with both neutrophiles andlymphocytes).Strategies involved either cellular or cell-freesystems, the former from healthy or from patholog-ical donators. Indirect effects in which the potencymodified the action of a stimulus on the target sys-tem were set apart from direct effects where thehomeopathic preparation acted on the target sys-tem directly.Replications were recognized when they investi-gated the same experimental setup (cell, enzyme,stimulant, noxa,
. . .
) with the same homeopathicremedy in high (but not necessarily identical)potency. They were operationally defined as ‘inde-pendent’ if the publication had a different firstauthor and less than half of their authors had pub-lished experiments with this model before.
130 C.M. Witt et al.
Table 1
The modified SAPEH (score for assessment of physical experiments on homeopathy)Item Points CriteriaObjectives
1 Explicit statement what problem or hypothesis was investigatedControls
Declared 1 Stated use of controlsAdequate +1 Succussed or correspondingly potentized solventInadequate
1 Not checking contamination, e.g. unsuccussedBlinding
1 Blinding of experimenter/testerRandomization
1 State of the art samples randomizationConsistency
1 Similar results in two or more experiments or test seriesExperiment standardization
Medium 1 Use of a buffer or buffered medium if necessaryIncubation 1 Standardized temperature and incubation timeStatistics
1 Statistical analysis declared or describedResults
1 Comprehensible presentation of results
Standardization: quality constructs built into the score. Modifications check for buffer andincubation.
it was noted whether the publications stated orimplied that the findings supported the existenceof effects of high potencies for at least one of thetested potencies, or, in multicenter trials, at leastone laboratory.
Modified SAPEH assessment
To provide a transparent and differentiated insightinto the strengths and weaknesses of the assessedresearch, we applied a modified version of theScore for Assessment of Physical Experiments onHomeopathy (SAPEH,Table 1). SAPEH had been developed to assess the quality of physical researchin homeopathy.
It is based on three qualityconstructs methodology, experiment standard-ization, presentation — that divide into 8 items,checkingfor10criteria.Eachitemscores1pointforan affirmative answer, except controls and experi-ment standardization with 2 points each.The methodology items check that the experi-mental design uses techniques to control factorsthat may cause bias (e.g. systematic or randomerrors). Mentioning controls scores 1 point that issubtracted again if their nature allows for chemicaldifferences to the potencies. Identical compositionis assumed if controls have undergone a simi-lar contaminant-affecting preparation (succussionor potentizing)
as the test potencies. It wouldearn 2 controls points, accepted are all mean-ingful descriptions such as ‘‘produced like theverum’’ or ‘‘succussed (shaken, vortexed, soni-cated,
. . .
) medium’’. Further methodology itemscover blinding (preventing handling differences andbias effects), randomization (to prevent system-atical errors), consistency (internal replications,ensuringtestsystemstability),andtheuseofstatis-tics.Experiment standardization was adapted to the
in vitro
field, instead of the somewhat unspecificoriginal criteria ‘external factors’ and ‘experimen-tal setup’ that can affect results, the item nowchecks for the use of a buffer or buffered medium,and for standardized temperature and incubationtime.The remaining communication about the exper-iment is covered by presentation of objectives andresults, which have to be reasonably detailed andunderstandable.The modified SAPEH should be read at item levelto assess an experiment. The total SAPEH score andits subscores support only rough global impressionsand should always be accompanied by score details.For the purposes of the present study, 6 or 7 pointswith controls of equal contamination would indi-cate a reasonable control for bias, and >7 points(including 2 for controls) would strengthen this.
We identified and obtained 75 publications
that fulfilled inclusion criteria, among them onesufficiently detailed correspondence.
Seventeenredundant publications were identified (Fig. 1): Three doctoral theses
were included thatcover and extend the content of eight omittedpapers:71—75, 76; 77, and 78, respectively.Two summaries
of otherwise included experimentswere ignored. From another summary
those parts

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