Novel strategies for the enhancement of the potency of nutraceuticals with low oral bioavailability and their application in novel functional foods for optimum protection of the aging brain
A research network sponsored by the German Federal Ministry of Education and Research
Curcumin is a nutraceutical intensively investigated for its potential use as a therapeutic or preventive agent against a number of degenerative diseases, including cancer and Alzheimer's disease. Curcumin is the coloring agent derived from the root of the plant Curcuma longa and gives the yellow color to the spice curry, in which it is found in significant amounts. It is also commonly used, under the designation "E 100", as a coloring agent by the food industry.
Because of its potent health beneficial activities, such as antiinflammatory, antioxidant, and anticancer effects, to name only a few, researchers have attempted to enhance the uptake and retention of the phytochemical in the body. Curcumin, however, remains a very difficult compound to detect in the body, because it is taken up into the body to a limited extent and subsequently rapidly metabolised and excreted from the organism. Hence, an important question in this context remains largely unanswered: Could the health beneficial activities of curcumin be enhanced if more of the active compound would reach the site of action, e.g. the brain?
To answer this and a number of related questions, Dr. Frank (University of Hohenheim) coordinated a research network consisting of five academic and five industry partners, which was financially supported by the German Federal Ministry of Education and Research with ca. € 1.5 M.
In the project, novel strategies to enhance the bioavailability and retention of curcumin in the organism were developed and researched for their impact on the pharmacokinetics, biological activities, and the safety of the nutraceutical. The novel micellar curcumin-formulations developed within this project were then tested for their biological activities and suitability as ingredients in a range of different functional foods.
The work packages of this research network were lead by Prof. Dr. Frank from the Institute of Biological Chemistry and Nutrition at Hohenheim University, PD Dr. Gunter Eckert from the Department of Pharmacology at the Johann-Wolfgang-Goethe University, Dr. Jakob Weissenberger from the Department of Neurosurgery at the University Hospital of the Johann-Wolfgang-Goethe University (Frankfurt/Main), Prof. Dr. Gerald Rimbach from the Institute of Human Nutrition and Food Science at Christian-Albrechts-University in Kiel, Prof. Dr. Tilman Grune from the Institute of Human Nutrition at the Friedrich-Schiller-University in Jena, Dariush Behnam, CEO of Aquanova AG, Dr. Josef Jandasek, Senior product developer at Raps GmbH & Co KG, Kalle Debus, Product Manager at Hassia Mineralquellen, Dr. Carola Funk, General Manager R&D at Kampffmeyer Food Innovation, and Julius Semrau of Schwartauer Werke.
Scientific papers related to this project
Flory, S., Männle, R. & Frank, J. (2021) The inhibitory activity of curcumin on P-glycoprotein and its uptake by and efflux from LS180 cells is not affected by its galenic formulation. Antioxidants 10: 1826, IF 6.312.
Flory, S., Sus, N., Haas, K., Jehle, S., Kienhöfer, E., Wähler, R., Adler, G., Venturelli, S. & Frank, J. (2021) Increasing post-digestive solubility of curcumin is the most successful strategy to improve its oral bioavailability: a randomized cross-over trial in healthy adults and in vitro bioaccessibility experiments. Mol Nutr Food Res 65: 2100613, IF 5.914.
Seiwert, N., Fahrer, J., Nagel, G., Frank, J., Behnam, D. & Kaina, B. (2021) Curcumin administered as micellar solution suppresses intestinal inflammation and colorectal carcinogenesis. Nutrition and Cancer 73: 686-693, IF 2.900.
Khayyal, M. T., El-Hazek, R. M., El-Sabbagh, W. A., Frank, J., Behnam, D. & Abdel-Tawab, M. (2018) Micellar solubilisation enhances the anti-inflammatory activities of curcumin and boswellic acids in rats with adjuvant-induced arthritis. Nutrition 54: 189-196, IF 3.420.
Frank, J., Schiborr, C., Kocher, A., Meins, J., Behnam, D., Schubert-Zsilavecz, M. & Abdel-Tawab, M. (2017) Transepithelial transport of curcumin in Caco-2 cells is significantly enhanced by micellar solubilisation. Plant Foods for Human Nutrition 72: 48-53, IF 2.276.
Dützmann, S., Schiborr, C., Kocher, A., Pilatus, U., Hattingen, E., Weissenberger, J., Gessler, F., Quick-Weller, J., Franz, K., Seifert, V., Frank, J. & Senft, C. (2016) Intratumoral concentrations and effects of orally administered micellar curcuminoids in glioblastoma patients. Nutr Cancer 68: 943-948, IF 2.322.
Kocher, A., Bohnert, L., Schiborr, C. & Frank, J. (2016) Highly bioavailable micellar curcuminoids accumulate in blood, are safe and do not reduce blood lipids and inflammation markers in moderately hyperlipidaemic individuals. Mol Nutr Food Res 60: 1555-1563, IF 4.551.
Bortel, N., Armeanu-Ebinger, S., Schmid, E., Kirchner, B., Frank, J., Kocher, A., Schiborr, C., Warmann, S.W., Fuchs, J. & Ellerkamp, V. (2015). Effects of curcumin in pediatric epithelial liver tumors: inhibition of tumor growth and alpha-fetoprotein in vitro and in vivo involving the NFkappaB and the beta-catenin pathways. Oncotarget, 6: 40680–40691, IF 6.359.
Hagl, S., Kocher, A., Schiborr, C., Kolesova, N., Frank, J., & Eckert, G. P. (2015) Curcumin micelles improve mitochondrial function in neuronal PC12 cells and brains of NMRI mice - Impact on bioavailability. Neurochemistry International 89: 234-242, IF 3.092.
Kocher, A., Hagl, S., Schiborr, C., Eckert, G. P., & Frank, J. (2015) Concentrations of total curcuminoids in plasma, but not liver and kidney, are higher in 18- than in 3-months old mice. NFS Journal 1: 3-8.
Kocher, A., Schiborr, C., Behnam, D., & Frank, J. (2015). The oral bioavailability of curcuminoids in healthy humans is markedly enhanced by micellar solubilisation but not further improved by simultaneous ingestion of sesamin, ferulic acid, naringenin and xanthohumol. J Funct Foods 14: 183-191, IF 4.480.
Hagl, S., Heinrich, M., Kocher, A., Schiborr, C., Frank, J., & Eckert, G. P. (2014). Curcumin micelles improve mitochondrial function in a mouse model of Alzheimer's disease. The Journal of Prevention of Alzheimer’s Disease 1: 80-83.
Chin, D., Hagl, S., Höhn, A., Huebbe, P., Pallauf, K., Grune, T., Frank, J., Eckert, G.P. & Rimbach, G. (2014). Adenosine triphosphate concentrations are higher in the brain of APOE3 compared to APOE4 targeted-replacement mice and can be modulated by curcumin. Genes & Nutrition 9: 397, IF 3.329.
Chin, D., Huebbe, P., Frank, J., Rimbach, G., & Pallauf, K. (2014). Curcumin may impair iron status when fed to mice for six months. Redox Biology 2: 563-569.
Schiborr, C., Kocher, A., Behnam, D., Jandasek, J., Toelstede, S., & Frank, J. (2014). The oral bioavailability of curcumin from micronized powder and liquid micelles is significantly increased in healthy humans and differs between sexes. Mol Nutr Food Res 58: 516-527, IF 4.909.
Schiborr, C., Schwamm, D., Kocher, A., Rimbach, G., Eckert, G. P., & Frank J. (2013) The senescence-accelerated mouse - prone 8 is not a suitable model for the investigation of cardiac inflammation and oxidative stress and their modulation by dietary phytochemicals. Pharmacol Res 74: 113-120, IF 4.436
Eckert, G. P., Schiborr, C., Hagl, S., Abdel-Kader, R., Müller, W. E., Rimbach, G., & Frank, J. (2013). Curcumin prevents mitochondrial dysfunction in the brain of the senescence-accelerated mouse - prone 8. Neurochemistry International 65: 595-602, IF 2.857.
Schrader, C., Schiborr, C., Frank, J. & Rimbach, G. (2011) Curcumin induces paraoxonase-1 in cultured hepatocytes in vitro but not in mouse liver in vivo. Brit J Nutr 105: 167-170, IF 3.072.
Schiborr, C., Eckert, G. P., Weissenberger, J., Müller, W. E., Schwamm, D., Grune, T., Rimbach, G. & Frank, J. (2010) Cardiac oxidative stress and inflammation are similar in SAMP8 and SAMR1 mice and unaltered by curcumin and Ginkgo biloba extract intake. Curr Pharmaceut Biotechnol 11: 861-867, IF 3.455.
Schiborr, C., Eckert, G. P., Rimbach, G. & Frank, J. (2010) A validated method for the quantification of curcumin in plasma and brain tissue by fast narrow-bore high-performance liquid chromatography with fluorescence detection. Anal Bioanal Chem 397: 1917-25, IF 3.841.
The research project in the media
Shooting in the lab
Monika Kovacsics and her camera team filmed in our laboratory and interviewed Prof. Frank about his curcumin research for the tv program Odysso. The piece was aired on SWR September 20, 2018. The media stream is available here.
Ernährung im Alter - Wie das Gehirn leistungsfähig bleibt
Bundesministerium für Bildung und Forschung, 2018
Hessischer Rundfunk | alles wissen | May 20, 2015
X:enius "Wunderwurzeln - Ingwer und Kurkuma“
ARTE | Monday, May 11, 2015 | 8:25 / 17:00
Available online
The Northern German television station NDR aired a segment on the health-beneficial properties of curcuma and its constitutent curcumin on January 15, 2013 as part of their programme Visite.
The journalist Judith König and her camera team visited our laboratory in Hohenheim and interviewed professor Frank, among other things, about recent human studies with curcumin, the poor bioavailability of the phytochemical, our BMBF-sponsored research project, and the micellar curcumin formulations developed by AQUANOVA.
The German government reported about our curcumin project in their first newspaper supplement „Deutschland aktuell“ published in 2015.
Dr. Jens Schmidt of the Federal Press Office talked with Professor Frank about nutrition research in general and his research on the health-beneficial effects of curcumin performed at the University of Hohenheim in cooperation with his partners and the problems that will have to be solved in future resarch to make the best use of the potential of this plant compound. The story and the interview (audio stream) with Professor Frank can be found on the website of the Federal Government.
In its October 2012 issue, Apotheken-Umschau published an article (in German) about the health-beneficial effects of Curcuma longa. [09/10/2012]
The newspaper Stuttgarter Zeitung published an article (in German) about the research network coordinated by Dr. Frank, which investigates novel strategies to improve the bioavailability of curcumin and their impact on the health beneficial properties of the nutraceutical. The online version of the article can be read here [05/01/2011].
The radio channel NDR Info aired a segment on the health beneficial properties of curcumin and the BMBF-funded research network coordinated by Dr. Frank in the show Logo - Das Wissenschaftsmagazin on January 7, 2011.
The Frankfurter Rundschau published an article about the joint-research project on curcumin and, in particular, the work packages of Drs Eckert and Weissenberger at the University of Frankfurt [27/12/2010].
The internet portal biotechnologie.de published a report about the BMBF-funded project on their website [21/12/2010].
The Frankfurter Neue Presse published an article about the work packages that are performed at the University of Frankfurt and investigate the effects of curcumin on mitochondrial function and tumor-suppression within the BMBF-funded research network [20/12/2010].
Press release of the University of Frankfurt, published 16/12/2010
Press release of the University of Hohenheim, published 08/12/2010
Participating researchers and industry partners
Coordinator: Prof. Dr. Jan Frank
University of Hohenheim
phone +49-711-459 24459
jan.frank@nutres.de
Prof. Dr. Gunter Eckert
Department of Pharmacology
Goethe University Frankfurt
Prof. Dr. Gerald Rimbach
Institute of Human Nutrition and Food Science
Christian-Albrechts University Kiel
Prof. Dr. Tilman Grune
Institute of Human Nutrition
University of Jena
Dr. Jakob Weissenberger
University Hospital Frankfurt/Main
Goethe University Frankfurt
Dariush Behnam
Aquanova AG, Darmstadt
Dr. Josef Jandasek
Raps GmbH, Kulmbach
Kalle Debus
Hassia Mineralquellen AG, Bad Vilbel
Dr. Carola Funk
Kampffmeyer Food Innovation, Hamburg
Julius Semrau
Schwartauer Werke, Bad Schwartau