Bioavailability is an important factor in the effectiveness of products, but it is not the only criterion used to compare and assess their efficacy. Various manufacturers recommend reducing the dosage of their products based on the presumed increased bioavailability of curcumin. However, research data does not support this approach, as most products increase the quantities of biologically insignificant Phase II metabolites rather than active metabolites or curcumin itself. Bioavailability is a crucial aspect of nutrient metabolism and should not be used solely for marketing and product promotion. 
Curcuminoids present an intriguing concept of pro-nutrients. After consumption, during Phase I of metabolism, several active metabolites are formed from curcumin, including dihydrocurcumin, tetrahydrocurcumin, hexahydrocurcumin, and octahydrocurcumin. As breakdown products of metabolism, ferulic acid and bicyclopentadione are produced. While it is proven that Phase I metabolites have favorable biological activity, the same cannot be said for curcumin glucuronides and sulfates—Phase II metabolism products—which have shown to be ineffective in independent studies. When enhancing the bioavailability of curcuminoids, it is essential to consider the pharmacological roles of its active metabolites. Simply increasing the bioavailability or presence of Phase II conjugates will not achieve the beneficial effects of curcumin; rather, an increase in unconjugated forms of curcuminoids is necessary. Modern biotechnologies for improving curcumin preparations raise questions about the ability to supply the body with unconjugated curcumin, as opposed to biologically inactive Phase II conjugates of curcuminoids. 
Extensive research and reviews on turmeric and curcumin are well-documented (1,2). The biological activity of curcumin is well-known; however, due to the detection of low levels of curcumin in the blood following its acute administration and in clinical studies with higher doses, various theories about the metabolic fate of curcumin have been developed. The aim to create curcumin products with improved absorption in the body and thus increased blood concentration has led to the development of various products on the market. Although the amount of curcumin itself is low in the blood, previous clinical research has revealed that most circulating curcumin is detected in the form of conjugates, such as glucuronides or sulfates (Phase II metabolism products, which have proven ineffective). Serum levels range from 22 to 41 ng/ml (3). This significant finding points to the rapid biotransformation of curcumin. Furthermore, research conducted on Phase II curcuminoid conjugates has shown that these conjugates, such as sulfates and glucuronides, have markedly low biological activity. To better understand the potential of Phase II curcuminoid metabolites, they were synthesized and their biological activity was studied against human cell lines, with comparisons made to curcumin. Research confirmed that curcumin glucuronides from Phase II do not exhibit significant biological activity, which is otherwise attributed to the three curcuminoids (4). On the other hand, Hassaninasab et al., in a 2011 PNAS paper, demonstrated the immediate biotransformation of curcuminoids via NADPH-dependent curcumin/dihydrocurcumin reductase into the most biologically active Phase I metabolite, tetrahydrocurcumin (5). Earlier studies have already established the strong biological activity of tetrahydrocurcumin, hexahydrocurcumin, and ferulic acid (6-8). Hexahydrocurcumin possesses fungicidal, antitumor, and antioxidant properties and promotes platelet aggregation (9-12). While curcumin itself has strong potential activity, its biological effects are realized through selective metabolites. Therefore, it is essential to highlight the importance of conversion pathways or the biological transformation of curcumin within the body. 
Arbitrarily increasing the bioavailability of curcumin does not necessarily result in a more valuable product. On the contrary, raising bioavailability beyond a certain level may have harmful effects, such as prolonging the QT interval of the heart wave (through inhibition of hERG channels) (13) or causing hemolysis. One of the approaches to improving absorption was the use of turmeric oil. However, turmeric oil has not yet proven to be safe for use in the human body, and Professor Janet Funk has demonstrated its detrimental effects on the protective roles of curcuminoids (14). A study on the bioavailability of Curcumin C3 Complex with BioPerine showed a 20-fold increase in absorption compared to regular forms of curcumin. An important fact is that, with C3 Complex, the active components, curcuminoids, are retained in their natural form and BioPerine is added to enhance bioavailability (active Phase I metabolites are formed).
After all, how will increasing the bioavailability of curcumin help if inactive metabolites are generated?
BioPerine is a 95% extract obtained from black pepper cultivated in the humid and nutrient-rich soils of southern India. The extract of piperine, known as BioPerine in its patented form, is the only black pepper extract that has supported its safety and efficacy for dietary use through clinical studies in the U.S. (GRAS status – Generally Recognized As Safe).
A clinical study from St. John Medical College, published in Planta Medica and conducted with healthy volunteers, demonstrated that the bioavailability of curcuminoids in Curcumin C3 Complex® can be increased 20-fold with the application of BioPerine (15). The study measured curcumin itself, not Phase II metabolites. BioPerine contains piperine, known to inhibit (stop) the formation of Phase II metabolites (16). It is also important to highlight piperine’s ability to induce thermogenesis. During thermogenesis, the demand for fresh nutrients in the body increases, which ultimately leads to better absorption in the intestines. 
Tufts University conducted a clinical safety trial of Curcumin C3 Complex and BioPerine. The combination of curcumin with BioPerine has proven safe for use with commonly prescribed medications such as flurbiprofen, acetaminophen, and midazolam (17). Data on drug interactions for other curcumin products is currently not available (at least not at this time). 
NutraCos, a highly respected European magazine among pharmacists, compared several branded curcumin products available in the EU and U.S. markets in one of its studies. More information and the full text are available at: članak – http://ita.calameo.com/read/0001513138bd69c3f32db
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17) Volak LP, Hanley MJ, Masse G, Hazarika S, Harmatz JS, Badmaev V, Majeed M, Greenblatt DJ, Court MH.
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