Peter Heusser

The German physician Samuel Hahnemann (1755–1843) established the basic principles of homeopathy as a medical specialty 200 years ago. Nowadays homeopathy is generally categorized as a method of complementary medicine, because its principles seem difficult to relate to modern western biomedicine and due to a different philosophical background. One important aspect is that Hahnemann ascribed the mode of action of homeopathic remedies—highly diluted potentized preparations (HDPPs)—to a non-physical force, called geistartig (literally translated as spirit-like). However, the term geistartig is nowadays difficult to understand and to translate, and it is open to misunderstanding. To build a bridge to today’s science, we aimed to clarify the meaning of geistartig. We therefore analyzed the complete body of Hahnemann’s publications and found that Hahnemann provided a consistent conceptualization of geistartig. The term geistartig encompasses the dynamic (force-like) effects of HDPPs and includes substance-specific gestalt-organizing effects, which differ from the known physical forces. A detailed analysis reveals that the hypothesis of such non-physical gestalt-organizing forces agrees with the concepts of modern biology and can also be tested empirically. We thus conclude that Hahnemann’s concept of the active principle of HDPPs can be related to contemporary research.

Objectives: There is a need for preclinical test systems to assess specific effects of homeopathic preparations in commonly available pharmaceutical form. We evaluated a plant bioassay regarding its capacity to distinguish homeopathically prepared pillules from placebo. Methods: Pea seed (Pisum sativum L. cv. Früher Zwerg) was soaked for 24 hours in water with dissolved homeopathic or placebo pillules. Plants germinated and grew in a standard cultivation substrate under controlled environmental conditions. Shoot length was measured 14 days after planting, and treatment groups were compared by analysis of variance (ANOVA). After a screening, three independent series of main experiments assessing the effects of Calcium carbonicum (12c, 30c, 200c) were performed with different experimenters in the same laboratory to assess reproducibility. The stability of the system was validated by systematic negative control experiments. Results: No false positive results were observed in the systematic negative control experiments. Placebo sucrose pillules did not influence shoot growth. A screening of 13 homeopathic preparations revealed Calcium carbonicum 12c to affect pea shoot growth (p = 0.02). In the first series of repetition experiments (n = 8), Calcium carbonicum 30c influenced shoot growth (p = 0.04). In series II and III (n = 2 ×10), no significant main effect could be observed. A meta-analysis of all data revealed the effect of Calcium carbonicum 12c and 30c to be dependent on the date of experiment and/or the experimental series. Conclusion: The system is suitable to test a common application form—sucrose pillules—of a homeopathic preparation without influence of the pharmaceutical carrier substance. We observed some evidence that Calcium carbonicum 12c and 30c exerted specific effects in this bioassay. Further optimization of this bioassay is necessary to be used in quality control or in investigating the biological or pharmaceutical mode of action of homeopathic preparations. Keywords: Homeopathy, anthroposophic medicine, homeopathic pillules, reproducibility, dwarf peas, plant bioassay, Calcium carbonicum

The placebo effect involves a complex network of psychological variables that are often disregarded by studies enquiring into this effect. It is hence little surprising that these psychological variables confound study outcomes and that experiments investigating the placebo effect often yield radically different results. The current article identifies three categories of psychological and methodological factors that are not systematically considered in placebo research: psychological confounds (Hawthorne effects and demand effects); methodological and data-analysis issues; and clinicians’ expectancy effects. These factors are not necessarily to be seen as mere artifacts, however, because they may constitute favorable components of the placebo effect. A set of benchmark criteria is therefore proposed to allow researchers to capitalize on these components during placebo research rather than have their results confounded by them; and to allow for a more reliable interpretation of study outcomes.

This issue of Forschende Komplementärmedizin/ Research in Complementary Medicine clearly demonstrates that complementary medicine provides globally applicable treatment options in different perspectives. The articles introduced in this issue not only reflect the demand for and the availability of effective alternative therapy for civilization diseases, such as depression, chronic low back pain, and other chronic or stress-dependent health problems, but they also point towards the need for a common conceptual ground for Eastern and Western medicine in order to overcome challenges in global health care.

While a variety of factors may play a role in fetal and neonatal deaths, postmaturity as a cause of stillbirth remains a topic of debate. It still is unclear, whether induction of labor at a particular gestational age may prevent fetal deaths.

Decision-making during pregnancy regarding different options of care can be difficult, particularly when risks of intervention versus no intervention for mother and baby are unclear. Unbiased information and support for decision making may be beneficial in these situations. The management of normal pregnancies at and beyond term is an example of such a situation. In order to determine the need to develop an evidence-based decision aid this paper searches, analyses and appraises patient decision aids and patient information leaflets regarding care options in cases of late term and post-term pregnancies, including complementary and alternative medicine (CAM). A literature search was carried out in a variety of lay and medical databases. Inclusion criteria: written information related to uncomplicated singleton pregnancies and targeted at lay people. Analysis and appraisal of included material by means of quality criteria was set up based on the International Patient Decision Aid Standards accounting for evidence-basing of CAM options. Inclusion of two decision aids and eleven leaflets from four decision aids and sixteen leaflets. One decision aid met the quality criteria almost completely, the other one only insufficiently despite providing some helpful information. Only one leaflet is of good quality, but cannot substitute a decision aid. There is an urgent need for the design of an evidence-based decision aid of good quality for late-term or post-term pregnancy, particularly in German language.

Macrophages are highly versatile cells that play an important role in tumour microenvironment. Tumour associated macrophages (TAMs) have been linked to both, good or bad prognosis of several cancer types depending on their number, composition and polarization. Viscum album lipophilic extract (VALE) contains several pentacyclic triterpenes known to modulate the activity of monocytes and other immune cells and to exhibit anticancer properties. In our in vitro study, we investigated the effect of tumour cell lines on macrophage polarization and monocyte chemotactic transmigration and examined the modulatory potential of VALE and its predominant triterpene oleanolic acid (OA). Human peripheral blood monocytes were differentiated into monocyte derived macrophages (MDM) using M-CSF and polarized into M1 by IFN-γ and LPS and into M2 macrophages by IL-4 and IL-13 or by co-culture with two different tumour cell lines. Polarized macrophages were subsequently treated with VALE or OA. Phenotypic markers and cytokines were assessed by flow cytometry and immunoanalysis. Migration of human peripheral blood monocytes induced by monocyte chemotactic protein-1 (MCP-1) or supernatants of different tumour cell lines under the influence of VALE or OA was measured in a chemotaxis transmigration assay. In vitro polarized M1 and M2 type macrophages revealed specific phenotypic patterns and tumour cell co-cultured MDM displayed ambiguous phenotypes with M1 as well as M2 associated markers. VALE and OA showed modest influence on cell surface marker profile and cytokine expression of tumour cell co-cultured macrophages. All tumour cell supernatants markedly enhanced the migratory activity of monocytes. VALE and OA significantly inhibited MCP-1 induced monocyte transmigration, whereas monocyte migration initiated by tumour cell derived supernatants was not affected. In our study we reconfirmed that co-culture with different tumour cell lines can result in a mixed macrophage phenotype with M1 as well as M2 patterns, a finding that is important for a better understanding of tumour microenvironment functions. Moreover, we demonstrated that VALE shows slight immunomodulatory effects on tumour cell co-cultured macrophages and modulates monocyte chemotactic transmigration in vitro, indicating promising possibilities of triterpenes from Viscum album L. to contribute in a multimodal concept of anti-cancer therapy in future. Our data contribute to an understanding of monocyte function and macrophage polarization in vitro and of the possibility to influence their behaviour by triterpene containing mistletoe extracts.