Bioraspoloživost kurkumina – ključna karakteristika za učinkovitost

Kurkuma (lat. Curcuma longa) is a spice obtained from the underground tree (rhizome) of the plant of the same name characteristic of India and Southeast Asia. Turmeric owes its characteristic yellow color to the polyphenol curcumin, a biologically active polyphenol from the curcuminoid group that is attributed with strong anti-inflammatory and antioxidant effects.

Curcumin (diferuloylmethane), is an active biological compound originating from turmeric, which in recent years has attracted the attention of the scientific community and the general population due to its numerous beneficial effects on health.

Posjeduje široki spektar bioloških učinaka: 

• • anti-inflammatory

• • antioxidant

• • anticarcinogenic

• • antimutagenic

• • anticoagulant

• • antibacterial, antifungal, antiviral

• • hypotensive and hypocholesterolemic effect

Furthermore, it can be useful for:

• • infertility

• • gastrointestinal diseases

• • diabetes

• • metabolic syndrome

• • neurodegenerativih  bolesti

• • dermatological diseases (spectrum of indications is shown in detail in Figure 1).

Physiologically, it is extremely well tolerated, it has negligible systemic toxicity even after high orally administered doses (up to 12 g).However, all these positive effects are difficult to express by using the usual forms and extracts of turmeric due to its very low solubility in water and limited bioavailability (1). Therefore, during the past decades, several groups of scientists are continuously engaged in the development of new bioavailable forms of curcumin, and among them the German group led by prof. Jan Frank from the University of Hohenheim from the Institute for Biological Chemistry and Nutrition Science.

His multi-year work on a project to study the specific characteristics of curcumin resulted in knowledge about the superiority of the highly bioavailable curcumin solubilized form in micelles. It has that shape 185x higher bioavailability compared to the native form (2), a radi se o zaštićenoj i patentiranoj supstanci NovaSOL^®.

The problem of bioavailability

Curcumin stands out as one of the most versatile natural ingredients with diverse biologically beneficial effects and pharmacological action. However, the native form is poorly soluble in water, unstable at the acidic pH that is characteristic of the stomach, and is very quickly metabolized in the liver and excreted in the feces, which is why the bioavailability of native curcumin is quite low.

Since the poor bioavailability limits the therapeutic benefit of curcumin, numerous attempts have been made to increase the absorption of the ingredient. Some of these approaches are combining curcumin with other substances due to increased bioavailability, for example with piperine (an alkaloid from black pepper) and turmeric ingredients that do not belong to the curcuminoid group, which resulted in a certain increase in bioavailability.

However, the greatest contribution to the bioavailability of curcumin was provided by the application of new technologies, as it brings new, highly useful forms of curcumin, and one of the newest and most effective forms is curcumin solubilized in micelles. In this way, it is possible for curcumin, which is normally insoluble in water, to become soluble in water.

Superior bioavailability of curcumin in micelles (NovaSOL^® Curcumin) dokazana je studijom u kojoj je sudjelovalo 23 ispitanika koji  su nasumičnim redom uzeli jednokratnu dozu  od 500 mg kurkuminoda u obliku nativnog kurkumina, mikroniziranog praha kurkumina ili  solubilizata kurkumina u micelama  (NovaSOL^® Curcumin). Upravo je oblik solubilizata kurkumina u micelama pokazao superiornu bioraspoloživost u odnosu na ostale oblike kurkumina, odnosno imao je  185 puta veću raspoloživost od nativnog kurkumina (Slika 1.). NovaSOL^® Curcumin sadržavao je standardiziranu količinu kurkuminoida (83 % kurkumina, 15 % demetoksikurkumina (DMC) i 2 % bisdemetoksikurkumina (BDMC)), a upravo su ti kurkuminoidi i izmjereni u plazmi zdravih dobrovoljaca, što dodatno potkrjepljuje poboljšanu apsorpciju. Nadalje, studija je pokazala kako nije bilo negativnog učinka na funkciju jetre i bubrega (2).

NovaSOL^® Curcumin predstavlja standard za bioraspoloživi kurkumin te su potrebne relativno male doze za postizanje blagotvornog učinka.  Primjerice, jedna likvidna kapsula, zbog 185 puta veće bioraspoloživosti micelarnog oblika kurkumina, odgovara primjeni 5800 miligrama nativnog kurkumina.

Solubilizacija i micele – rješenje za superiornu bioraspoloživost kurkumina

Solubilization is a phenomenon by which otherwise insoluble substances can be dissolved in a surfactant micellar solution in water.Micelles are particles that behave in aqueous solutions in such a way that the hydrophilic ends are directed towards the surface of the micelle, while the hydrophobic ends are directed towards the center. In this way, it is ensured that a component that is normally insoluble, such as curcumin, becomes soluble in water.

In order to obtain a crystal-clear curcumin solubilizer, it is essential to use a surfactant - a substance that reduces surface tension, and the oleic acid salt (polysorbate) is used as a suitable and effective substance. In this way, curcumin is completely unmodified, its original structure is unchanged, and at the same time its availability for the body is significantly changed.

Characteristics of micelles:

• • 185x higher bioavailability of curcumin compared to the native form

• • 100% soluble in water

• • they have an average diameter of 30 nm

• • thermally, mechanically and pH stable

Continuous scientific work on bioavailability research

A group of scientists led by prof.During the last few years, Jan Frank has published several scientific studies in which the bioavailability of the micellar form of curcumin was investigated, most often on cancer cells. Below is a brief overview of the latest research:

• • Transepithelial transport of curcumin in colon cancer cells (Caco-2)
    The study compared the availability of native curcumin compared to curcumin in micelles on a colon cancer cell model. A significantly better availability of micellar curcumin compared to the native form was found. After 180 minutes, there was 9.5 times more curcumin on the basolateral side after application of curcumin in micelles compared to the native form (4).

• • Primjena kurkumina kod pedijatrijskih epitelnih karcinoma jetre  
    U ovoj studiji kurkumin u micelama istraživan je in vitro and in vivo. Značajne koncentracije kurkuminoida pronađene su u krvi, lizatima organa i tumorskom tkivu. Ujedno, znanstvenici su  zaključili kako kurkumin u micelama u kombinaciji s cisplatinom može biti obećavajuća terapija kod pedijatrijskog hepatocelularnog karcinoma (5).

• • Orally administered curcuminoids in patients with glioblastoma
    The research was conducted on 13 patients with glioblastoma who took 70 mg of curcumin in micelles before neurosurgery. After the procedure, a high concentration of curcumin was detected in the tumor tissue, and the average serum concentration was 253 ng/mL (6).

• • Curcumin in micelles and influence on mitochondrial function of PC12 neuronal brain cells
    Primjena kurkumina u micelama ukazala je na potencijal prevencije mitohondrijske disfunkcije  kod starenja mozga i neurodegeneracije na modelu laboratorijskih životinja (7).

Author: Assoc. Ph.D.Sc. Darija Vranešić Bender, clinical nutritionist

Literature:

1. Hani U, Shivakumar HG. Solubility enhancement and delivery systems of curcumin a herbal medicine: a review. Curr Drug Deliv. 2014;11(6):792-804.

2. Schiborr C, Kocher A, Behnam D, Jandasek J, Toelstede S, Frank J. 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. 2014;58(3):516-27.

3. Aggarwal BB, HarikumarKB Potential Therapeutic Effects of Curcumin, the Anti-inflammatory Agent, Against Neurodegenerative, Cardiovascular, Pulmonary, Metabolic, Autoimmune and Neoplastic Diseases. Int J Biochem Cell Biol. 2009; 41(1): 40–59.

4. Frank J, Schiborr C, Kocher A, Meins J, Behnam D, Schubert-Zsilavecz M,, Abdel-Tawab M.Transepithelial Transport of Curcumin in Caco-2 Cells Is Significantly Enhanced by Micellar Solubilization. Plant Foods Hum Nutr. 2016 Nov 29

5. Bortel N, Armeanu-Ebinger S, Schmid E, Kirchner B, Frank J, Kocher A, Schiborr C, Warmann S, Fuchs J, Ellerkamp V. 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. 2015 1;6(38):40680-91.

6. 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. Intratumoral Concentrations and Effects of Orally Administered Micellar Curcuminoids in Glioblastoma Patients. Nutr Cancer. 2016;68(6):943-8.

7.Hagl S, Kocher A, Schiborr C, Kolesova N, Frank J, Eckert GP. Curcumin micelles improve mitochondrial function in neuronal PC12 cells and brains of NMRI mice – Impact on bioavailability.Neurochem Int. 2015;89:234-42.