In Natural Product INSIDER's article, “Curcumin’s popularity ups and downs,” Chase Shryoc noted that the supplement industry can better market the bioavailability of enhanced absorption curcumin products. He observed that comparing “X” times bioavailability of one product as opposed to “X + 1” times for other products is “confusing and meaningless to consumers.” He further noted that a better way of comparing products would be to show how much of an active ingredient is absorbed by stating the number of curcuminoids per ml of plasma. This simple statement raises several issues.
Free bioactive curcumin in the blood (plasma) is the best indicator of absorption and bioavailability. When curcumin is absorbed, much of it is converted to the biologically inactive forms curcumin sulfate and curcumin glucuronide. Most curcumin pharmacokinetic studies in humans designed to assess curcumin absorption measure total (free plus conjugated) curcumin, and not free, bioactive curcumin in the blood because enzymatic hydrolysis of plasma samples is employed prior to extraction and analysis. Enzymatic hydrolysis frees curcumin from its inactive forms. Therefore, the amount of free bioactive curcumin is unknown and cannot be determined. Therefore, products that use enzymatic hydrolysis to determine blood levels greatly inflate the results of their studies regarding curcumin absorption, and their reports of enhanced curcumin absorption can be misleading. What is important is the amount of free, un-metabolized and biologically active curcumin in the blood, and not the amount of biologically inactive conjugates of curcumin [Biomed J Sci Tech Res. 2019; DOI: 10.26717/BJSTR.201912.002289].
The dietary supplement industry must adhere to the highest standards of appropriate pharmacokinetic practice, utilizing the same techniques and methods for assessing blood levels of bioactive constituents as are used in the pharmaceutical industry. Hydrolysis of plasma samples prior to extraction and analysis is not an accepted technique in the pharmaceutical industry, nor should it be in the dietary supplement industry. Only then will consumers have a clear understanding of the efficacy of any given curcumin product.
A second issue in comparing various curcumin products formulations is the wide disparity in the amount of curcumin administered, which can range from 65 mg to as high as 1,000 mg. Plasma levels of free curcumin, and its inactive conjugates and metabolites are not only impacted by the relative ability of a given product to be absorbed, but also the relative dose of curcumin administered. Two common pharmacokinetic terms are used to express absorption. The Cmax is the maximum (peak) concentration of a substance such as curcumin, and the area under the curve (AUC) over a finite period of time provides information on the amount (extent) of curcumin absorbed.
Although the Cmax is related to absorbability, it does not tell how much curcumin was absorbed, while AUC provides a direct measurement of bioavailability. Unfortunately, claims of enhanced absorbability in marketing materials are sometimes made based on the Cmax values expressed as ng/ml between a given product and unformulated standard 95 percent curcumin or with other formulations of curcumin. When comparing bioavailability of various products, to account for differences in the degree to which the absorption of curcumin is enhanced by the product formulation as well as differences in the amount of curcumin administered, the plasma curcumin data for each product should be normalized by expressing it as the AUC/mg of administered curcumin. It should also be re-emphasized that the plasma samples must be directly extracted without hydrolysis prior to analysis, and the samples analyzed by the most sensitive methods possible such as high-performance liquid chromatography (HPLC) coupled with tandem or quadrupole mass spectrometry.
As pointed out by Shryoc in his article, several enhanced absorption formulations for curcumin have been developed, using various excipients. However, the most effective products to date in terms of absorption of curcumin rely on curcumin liquid droplet nanomicellar formulation technology (J Am. Coll Nutr. 2018; 37: 51-59). When plasma curcumin absorption data for these formulations are expressed as AUC/mg administered curcumin and compared with similarly expressed absorption data of curcumin from a wide variety of other products, the results can in fact be expressed as “X” times greater. Stratum Nutrition and Boston BioPharm have recently completed a study comparing the effects of enzymatic hydrolysis versus no hydrolysis on curcumin determination in human plasma following oral administration. The results indicated the depth of the issue, and the manuscript detailing the results is in the process of being submitted for publication. For consumers to have trust in the industry and in the product claims made, accuracy, veracity and transparency are paramount.
Sidney J. Stohs, Ph.D. is executive vice president for scientific affairs at Boston Biopharm LLC. He is Dean Emeritus of the Creighton University Medical Center School of Pharmacy and Health Professions, Omaha, Nebraska. He served as the senior Vice president for research and development and vice president of scientific affairs for AdvoCare International, a nutrition and wellness company. He has over 400 peer reviewed articles published in scientific and professional journals and books related to nutrition, toxicology, chemoprevention, pharmacology and education.