We conduct research according to highest scientific standards
Our clinical studies prove the efficacy of our pharmaceuticals, and our preclinical studies investigate the mode of action of our medicines in detail.
We meet our research ambitions through ground-breaking technologies and a global network of leading scientists following the principles of evidence-based medicine.
Scientific studies are conducted to prove the efficacy and safety of Heel medicines. Our clinical research programs build upon the evidence-based medicine model. In cooperation with international research partners, our research team designs and executes randomized, controlled, blinded clinical trials in strict accordance with worldwide ethical and scientific research standards. Each study is carefully designed and well-described. Validated outcomes are selected to ensure a study will be robust and create additional valuable evidence.
We actively involve independent medical and scientific experts in developing study designs and interpreting the results. The studies are published in recognized peer reviewed medical journals. They are scientifically recognized as certifying the efficacy and effectiveness of Heel's drugs and are included in several medical guidelines.
The Traumeel® Acute Ankle Sprain Study (TAASS) has reported that Traumeel® topical application is as effective in reducing mild to moderate post-injury pain and improving ankle mobility as diclofenac gel¹.
In the Management of Osteoarthritis of the Knee with Zeel® and Traumeel® study (MOZArT), co-administered intra-articular injections of Traumeel® and Zeel T® were superior to saline control injections in reducing moderate to severe pain in the affected knee. The effect size was comparable to the standard-of-care treatments, such as intra-articular hyaluronates, intra-articular corticosteroids, or oral diclofenac².
A multicenter, randomized double-blind active-comparator clinical trial has demonstrated that Vertigoheel® is as effective in reducing frequency, duration, and intensity of vertigo attacks as betahistine³. In another randomized double-blind active-comparator trial, Vertigoheel® was as effective as Ginkgo biloba in reducing frequency, duration, and intensity of vertigo episodes in patients older than 60 years⁴.
In an acute stress setting, a prospective, randomized, double-blind, placebo-controlled study in healthy subjects [probands] (NEUPRO), Neurexan® reduced stress biomarkers, such as salivary cortisol and plasma adrenaline⁵.
The NEURIM trial (Neuronal Correlates of Neurexan® Action in Mildly to Moderately Stressed Probands Predicted by Functional Magnetic Resonance Imaging), a randomized, double-blind, placebo-controlled, cross-over clinical trial, explored effects of Neurexan® on brain activity. It demonstrated that Neurexan® reduced stress-induced brain activation in multiple regions important in processing social stress⁶.
Heel medicines, such as Traumeel®, were included in the recommendation of the Spanish Consensus Statement for the treatment of muscle tears in sport⁷,⁸. Traumeel® is also included in the German National Anti-Doping Agency’s (NADA) list of permitted drugs⁹. Vertigoheel® reduced vertigo symptoms to the same extent as standard treatments and was included in the German acute vertigo treatment S3 guidelines to general practitioners¹⁰.
Preclinical research is used to investigate the biological effects of Heel medicines.
Heel medicines are multicomponent combinations of natural ingredients in low concentrations designed to have multiple targets; therefore, their modes of action are much broader compared to synthetic drugs. We use modern technologies – amongst others also transcriptomics – to explore biological activity. This is an excellent method for investigating the effects of our multi-target drugs.
Research work involving internationally standardized technology platforms provides insights into the biological properties of our drugs from the perspective of systems biology. Independent international research laboratories have reported significant results using these modern laboratory methods. The study results are presented at scientific conferences, where they have attracted considerable interest, and are published in respected peer-reviewed scientific journals.
Traumeel® has demonstrated significant anti-inflammatory and immunomodulatory action in cultures of human blood and gut cells, which are involved in immune response and inflammation. Traumeel® regulated inflammation by reducing release of proinflammatory cytokines (IL-1β, TNF-α, and IL-8) and promoting release of anti-inflammatory mediators (TGF-β). In animal models of inflammation Traumeel® significantly reduced local inflammation, inflammation-induced swelling, and decreased production of proinflammatory cytokine IL-6. It has also demonstrated an antioxidative effect similar to that of vitamin E. The latest studies showed that Traumeel® significantly changed gene expression in wounded tissues and promoted inflammation resolution in an animal model22.
These results are congruent with clinical evidence that therapy with Traumeel® improves recovery from various types of musculoskeletal injuries, including the associated pain and swelling.
Reviewed by Schneider (2011)11, Cesnulevicius (2011)12, van Haselen (2017)13 and Wolfarth (2022)22.
A single dose of Neurexan® can significantly change the EEG wave signature of several brain areas in animals including δ-, θ-, and α2 waves supporting the calming effect of Neurexan® in general17 and mitigating acute stress-induced insomnia23. In exercise-stressed sled dogs, compared to placebo, Neurexan® significantly reduced cortisol, a biomarker for acute stress, and significantly decreased levels of gastrin, a hormone that can cause gastritis and gastric ulcers24. In humans, Neurexan® significantly reduced the increase in β2 waves in the brain, which are associated with stress-induced anxiety18. More recent fMRI studies in healthy volunteers demonstrated that Neurexan® reduces brain activity in regions associated with the stress response both at rest and when performing a task6. It showed multitarget effects of Neurexan® that reduces the brain’s response to negative emotional stimuli6, decreases the susceptibility to destruction25, reduces vigilance level26 and stress response after stress exposure27, and improves stress response regulation in resting state28.
Brain studies in animals and humans using EEG (electroencephalogram) – Dimpfel et al. (2012, 2019)17,18, Davis et al. (2022)23, Chand et al. (2022)26 and fMRI (functional Magnetic Resonance Imaging) – Herrmann et al. (2020, 2022)6, 27, Mayer et al. (2021)25, Chand et al. (2022)28.
Vertigoheel® demonstrated a significant effect for dilating blood vessels by modulating the key enzymes involved in smooth muscle activity in the vascular wall. Intravital microscopy of the micro blood vessels of the skin of patients with mild vertigo showed that Vertigoheel® also can improve microcirculation via a number of different mechanisms. These effects on blood vessels may at least partially explain the positive clinical outcomes in patients with different types of vertigo. In the more recent preclinical studies, Vertigoheel® significantly increased activity in brain regions involved in memory processing and learning,29 and improved central vestibular compensation30.
Preclinical study measuring the vasorelaxant effect – Heinle et al. (2010)14, intravital microscopy in patients with mild vertigo – Klopp et al. (2005)15, studies in animals – Dimpfel et al. (2019)29 and Hatat et al. (2022)30, and meta-analysis of clinical trials – Schneider et al. (2005)16.
1. González de Vega C, Speed C, Wolfarth B, González J. Traumeel vs. diclofenac for reducing pain and improving ankle mobility after acute ankle sprain: A multicentre, randomised, blinded, controlled and non-inferiority trial. Int J Clin Pract. 2013;67(10):979-989. doi:10.1111/ijcp.12219.
2. Lozada CJ, del Rio E, Reitberg DP, Smith RA, Kahn CB, Moskowitz RW. A double-blind, randomized, saline-controlled study of the efficacy and safety of co-administered intra-articular injections of Tr14 and Ze14 for treatment of painful osteoarthritis of the knee: The MOZArT trial. Eur J Integr Med. 2017;13(July):54-63. doi:10.1016/j.eujim.2017.07.005.
3. Weiser M, Strösser W, Klein P. Homeopathic vs Conventional Treatment of Vertigo. Arch Otolaryngol Neck Surg. 1998;124(8):879. doi:10.1001/archotol.124.8.879.
4. Issing W, Klein P, Weiser M. The homeopathic preparation Vertigoheel® versus Ginkgo biloba in the treatment of vertigo in an elderly population: A double-blinded, randomized, controlled clinical trial. J Altern Complement Med. 2005. doi:10.1089/acm.2005.11.155.
5. Doering BK, Wegner A, Hadamitzky M, Engler H, Rief W, Schedlowski M. Effects of Neurexan ® in an experimental acute stress setting — An explorative double-blind study in healthy volunteers. Life Sci. 2016;146:139-147. doi:10.1016/j.lfs.2015.12.058.
6. Herrmann L, Vicheva P, Kasties V, et al. fMRI Revealed Reduced Amygdala Activation after Nx4 in Mildly to Moderately Stressed Healthy Volunteers in a Randomized, Placebo-Controlled, Cross-Over Trial. Sci Rep. 2020;10(1):3802. doi:10.1038/s41598-020-60392-w.
7. Fernandez-Jaén TF, Rey GÁ, Cuesta JA, et al. Spanish Consensus Statement. Orthop J Sport Med. 2015;3(12):232596711562243. doi:10.1177/2325967115622434.
8. Del Valle Soto M, Díaz FJ, Marqueta PM, Parenteau CR, Vicente JMR, Fernández LS. Consenso sobre utilización de la vía parenteral en el deporte. Utilización de medicación homeopática, terapias biológicas y biorreguladoras. Documento de Consenso de la Federación Española de Medicina del Deporte. Arch Med del Deport. 2013;30(153):8-13.
9. (NADA) NADAD. Beispielliste zulässiger Medikamente 2022. https://www.nada.de/fileadmin/user_upload/nada/Downloads/Listen/NADA_Beispielliste_zulaessiger_Medikamente_2022.pdf Published 2022.
10. DEGAM Deutsche Gesellschaft für Allgemeinmedizin und Familienmedizin e.V. Akuter Schwindel in der Hausarztpraxis, S3-Leitlinie. DEGAM Leitlinie Nr 17. 2016.
11. Schneider C. Traumeel: an emerging option to nonsteroidal anti-inflammatory drugs in the management of acute musculoskeletal injuries. Int J Gen Med. March 2011:225. doi:10.2147/IJGM.S16709.
12. Cesnulevicius K. The Bioregulatory Approach to Work-related Musculoskeletal Disorders: Using the Multicomponent Ultra low–dose Medication Traumeel to Target the Multiple Pathophysiological Processes of the Disease. Altern Ther Health Med. 2011.
13. van Haselen R. An integrative review of the evidence on the efficacy of the antihomotoxic medication Traumeel [In Russian]. Farmatsiya (Moscow). 2017.
14. Heinle H, Tober C, Zhang D, Jäggi R, Kuebler WM. The low-dose combination preparation Vertigoheel activates cyclic nucleotide pathways and stimulates vasorelaxation. Clin Hemorheol Microcirc. 2010;46(1):23-35. doi:10.3233/CH-2010-1330.
15. Klopp R, Niemer W, Weiser M. Microcirculatory effects of a homeopathic preparation in patients with mild vertigo: an intravital microscopic study. Microvasc Res. 2005;69(1-2):10-16. doi:10.1016/j.mvr.2004.11.005.
16. Schneider B, Klein P, Weiser M. Treatment of vertigo with a homeopathic complex remedy compared with usual treatments: A meta-analysis of clinical trials. Arzneimittel-Forschung/Drug Res. 2005. doi:10.1055/s-0031-1296821.
17. Dimpfel W, Roeska K, Seilheimer B. Effect of Neurexan on the pattern of EEG frequencies in rats. BMC Complement Altern Med. 2012;12(1):126. doi:10.1186/1472-6882-12-126.
18. Dimpfel W. Effects of Neurexan on Stress-Induced Changes of Spectral EEG Power: A Double-Blind, Randomized, Placebo-Controlled, Crossover Exploratory Trial in Human Volunteers. World J Neurosci. 2019;09(03):100-112. doi:10.4236/wjns.2019.93007.
19. St. Laurent G, Seilheimer B, Tackett M, et al. Deep Sequencing Transcriptome Analysis of Murine Wound Healing: Effects of a Multicomponent, Multitarget Natural Product Therapy-Tr14. Front Mol Biosci. 017;4(AUG):1-12. doi:10.3389/fmolb.2017.00057.
20. Wronski S, Dannenmaier J, Schild S, et al. Engystol reduces onset of experimental respiratory syncytial virus-induced respiratory inflammation in mice by modulating macrophage phagocytic capacity. Bose S, ed. PLoS One. 2018;13(4):e0195822. doi:10.1371/ journal.pone.0195822.
21. Jordan PM, van Goethem E, Müller AM, Hemmer K, Gavioli V, Baillif V, Burmeister Y, Krömmelbein N, Dubourdeau M, Seilheimer B, Werz O. The Natural Combination Medicine Traumeel (Tr14) Improves Resolution of Inflammation by Promoting the Biosynthesis of Specialized Pro-Resolving Mediators. Pharmaceuticals. 2021; 14(11):1123. https://doi.org/10.3390/ph14111123.
22. Wolfarth B, Speed C, Raymuev K, Vanden Bossche L, Migliore A. Managing pain and inflammation associated with musculoskeletal disease: time for a change?. Curr Med Res Opin. 2022;38(10):1695-1701. doi:10.1080/03007995.2022.2108618.
23. Davis CJ, Schmidt MA, Hemmer K, Krömmelbein N, Seilheimer B. Multicomponent drug Neurexan mitigates acute stress-induced insomnia in rats. J Sleep Res. 2022;31(5):e13550. doi:10.1111/jsr.13550.
24. Keller A, Conradi J, Weber C, Failing K, Wergin M. Efficacy of Nx4 to Reduce Plasma Cortisol and Gastrin Levels in Norwegian Sled Dogs During an Exercise Induced Stress Response: A Prospective, Randomized, Double Blinded, Placebo-Controlled Cohort Study. Front Vet Sci. 2021;8:741459. Published 2021 Oct 26. doi:10.3389/fvets.2021.741459.
25. Mayer K, Krylova M, Alizadeh S, et al. Nx4 Reduced Susceptibility to Distraction in an Attention Modulation Task. Front Psychiatry. 2021;12:746215. Published 2021 Nov 29. doi:10.3389/fpsyt.2021.746215.
26. Chand T, Alizadeh S, Jamalabadi H, et al. EEG revealed improved vigilance regulation after stress exposure under Nx4 – A randomized, placebo-controlled, double-blind, cross-over trial [published correction appears in IBRO Neurosci Rep. 2022 Jan 05;12:81]. IBRO Neurosci Rep. 2021;11:175-182. Published 2021 Sep 25. doi:10.1016/j.ibneur.2021.09.002.
27. Herrmann L, Kasties V, Boden C, et al. Nx4 attenuated stress-induced activity of the anterior cingulate cortex – A post-hoc analysis of a randomized placebo-controlled crossover trial. Hum Psychopharmacol. 2022;37(5):e2837. doi:10.1002/hup.2837.
28. Chand T, Alizadeh S, Li M, et al. Nx4 Modulated Resting-State Functional Connectivity Between Amygdala and Prefrontal Cortex in a Placebo-Controlled, Crossover Trial. Brain Connect. 2022;12(9):812-822. doi:10.1089/brain.2021.0189.
29. Dimpfel W, Seilheimer B, Schombert L. In Vitro Hippocampal Electrophysiology and in Vivo Quantitative EEG Revealed Robust Neurophysiological Effects of the Antivertigo-Agent Vertigoheel® in a Rat Study. Neuroscience and Medicine. 2019; 10: 407-425. doi: 10.4236/nm.2019.104030.
30. Hatat B, Boularand R, Bringuier C, et al. Vertigoheel improves central vestibular compensation after unilateral peripheral vestibulopathy in rats. Front Neurol. 2022;13:969047. Published 2022 Sep 23. doi:10.3389/fneur.2022.969047.