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Pharmacokinetic (PK) studies are presented below. Those conducted with generic curcumin preparations are presented first, followed by studies conducted with BCM-95.


Initial experiments conducted with rats on the uptake distribution and excretion of curcumin indicated that the compound was poorly absorbed. Curcumin administered orally to Sprague Dawley® rats at 1 g/kg resulted in 75% being excreted in the feces and only negligible amounts excreted in the urine. Metabolites of curcumin were identified in studies in which the test material was administered intravenously or intraperitoneally. The major metabolites, observed in bile, were glucuronides of THC and hexahydrocurcumin (HHC), while a lesser metabolite was dihydroferulic acid, followed by traces of ferulic acid. Experiments with mice found the major metabolites to be curcumin-glucuronide, dihydrocurcumin-glucuronide, THC-glucuronide, and THC. In another study, rat liver tissue contained the metabolites THC, HHC, and octahydrocurcumin (OHC). These studies have been reviewed by Goel and colleagues.2

PK studies in humans showed a similar low degree of absorption following oral administration. A study in which 2 g curcumin powder (four capsules of 500 mg each; Sami Chemicals and Extracts; Bangalore, India) was given to 10 healthy male volunteers found that serum levels of curcumin were either very low or undetectable with a Cmax of 6 ± 5 ng/mL at one hour. The mean AUC(0-tn), which was calculated using a trapezoidal method, was found to be 4 ng/h/mL.43

In another PK study with men and women with various cancers (N = 25; median age: 60 years; range: 36-77 years), curcumin was observed in the plasma of those who consumed oral doses of 4, 6, and 8 g, but not in the plasma of those who consumed lower doses of 0.5 or 2 g. (The test material was 99.3% curcumin [diferuloylmethane], provided by Yung-Shin Pharmaceutical Co.; Taichung, Taiwan.) The presence of curcumin in plasma peaked between 1.5 and 2 hours and gradually declined over 12 hours. The Cmax increased along with the dose of curcumin, from 0.51 ± 0.11 µM following the 4-g dose to 1.77 ± 1.87 µM following the 8-g dose. The AUC(0-24h), which was calculated using the linear trapezoidal technique, was also enhanced with the increase in dose, from 2.55 ± 1.76 nmol/h/mL following administration of 4 g to 13.74 ± 5.63 nmol/h/mL following 8 g. A repetition of this protocol with two patients who had been taking curcumin for more than a month resulted in similar results, indicating that repeat dosing did not change the absorption profile.44

A dose-escalation study examined the pharmacokinetics of curcuminoids using 500-mg capsules containing 450 mg curcumin, 40 mg demethoxycurcumin, and 10 mg bisdemethoxycurcumin (Curcumin C3 Complex® provided by Sabinsa Corporation; East Windsor, New Jersey).45 The study included 15 patients (men and women, ages 50-74) with advanced colorectal cancer who were administered doses of 0.45 g to 3.6 g curcumin (one to eight capsules) daily for up to four months. The levels of curcuminoids were determined in plasma, urine, and feces. Metabolic conjugates of curcuminoids were analyzed by incubating the samples with glucuronidase and sulfatase enzymes, which removed the glucuronide and sulfate groups from the curcuminoids revealing the native compounds. The study found that curcumin was not detected in the plasma of patients that received doses lower than 3.6 g curcuminoids. Following ingestion of a single dose of 3.6 g curcuminoids, unconjugated curcumin was detected in plasma samples of half of the patients. In those patients, curcuminoids were measured in serum samples taken 30 minutes and one hour after consumption, with a mean concentration of 11.1 ± 0.6 nmol/L. When the plasma samples were subjected to enzymatic treatment, curcuminoids were found in measurable amounts in all patients who took the 3.6-g dose. The mean amounts of curcumin sulfate and curcumin glucuronide in pooled plasma samples were 8.9 ± 0.7 nmol/L and 15.8 ± 0.9 nmol/L, respectively. There were no obvious differences in the levels of the conjugates in patients for which the parent curcumin was detected, compared to those for which it was not detected.

BCM-95 (Curcugreen)

A series of experiments have been conducted exploring the bioavailability of BCM-95 comparing it to that of standard curcumin. These studies are described in the following sections.

Ex vivo Pharmacokinetics

The bioavailability of isolated curcumin, curcumin in turmeric powder, and curcumin in BCM-95 were compared in water and traditional food-based vehicles using a non-everted rat intestinal sac model.46 As an initial step, the solubility of curcumin and BCM-95 in solutions of water, clarified butter (called ghee in traditional Ayurvedic medicine in India), and corn (Zea mays, Poaceae) oil were compared. BCM-95 was significantly more soluble in water than curcumin (5.4 times, P < 0.005). Both curcumin and BCM-95 were more soluble in clarified butter and corn oil compared to water, without any significant differences between them.

The degree of permeability of curcumin through the intestine was in agreement with the solubility findings. Maximum permeability was obtained from the addition of corn oil (13.4%), followed by clarified butter (9.82%), milk (4.24%), and the least was with water (1.66%). The permeability of the curcumin present in turmeric powder and in BCM-95 was significantly greater than the permeability of curcumin alone. There were no significant differences in total permeability between curcumin in turmeric and BCM-95. The authors of the study stated that this result suggested the presence of volatile oil components in both turmeric powder and in BCM-95 was responsible for the enhanced permeability. The rate of permeability (flux) through the membrane was greater for curcumin in turmeric powder compared to curcumin in BCM-95 (P < 0.05). Because of this finding, the authors suggested that there may be components such as sugars in turmeric powder, in addition to the essential oil, that assist with the speed of the flow through the membrane.

Animal Pharmacokinetics


Feeding experiments conducted with rats explored the effect of the addition of the essential oil on the absorption of curcuminoids. Curcuminoids with and without the essential oil were administered orally to the animals in their food in doses of 0.5, 1.5, and 3.0 mg/kg body weight. Animals administered their normal diet were included as controls. The study used albino rats (male and female; 100 to 120 g body weight), divided into seven groups with six animals per group. After 24 hours, the fecal matter from the animals was collected, dried, and weighed. The presence and quantity of curcumin in the fecal matter was detected using a spectrophotometric method from the Food Chemicals Codex (FCC). The percentage of absorbed curcumin was determined as the amount fed minus the amount in fecal matter. The amount of standard curcumin that was absorbed was approximately 58%, regardless of the dose. The amount of curcumin absorbed from the curcumin/essential oil mixture was approximately 96%. In summary, this study showed that mixing curcumin with the essential oil from turmeric enhanced the absorption and thus the bioavailability of curcumin.47


The oral bioavailability of BCM-95 (designated as NMXCC-95) in dogs§ was assessed using a crossover study design with a one-week washout between tests. The study included six healthy male and female adult dogs (12-15 kg body weight; three to four years old). The animals were divided into two groups of three dogs each and administered BCM-95 or curcuminoids (2 g) following a 12-hour fast. Blood samples were taken before administration (time 0) and at 1, 2, 3, 4, 5, 6, and 8 hours post-dose. Plasma samples were weighed, extracted with ethyl acetate, evaporated, then reconstituted in methanol and analyzed by high-performance liquid chromatography (HPLC) with detection at 420 nm. The resulting Cmax was significantly (3x) greater with BCM-95; approximately 300 ng/g compared to 99 ng/g for curcumin (P < 0.5).** The AUC(0-8h) also was significantly greater, roughly 1400 ng/h/g compared to 200 ng/h/g. The bioavailability of BCM-95 was thus approximately seven times greater than curcumin when measured as AUC.48

Turmeric Curcuma longa
Photo ©2019 Steven Foster


Human Pharmacokinetics

A pilot PK study was conducted with 15 healthy human volunteers, men and women ages 25 to 45, divided into two groups: curcumin (n = 8) and BCM-95 (n = 7).49 The subjects were instructed to avoid turmeric-containing foods 24 hours before and during the study. Curcumin (Sigma-Aldrich Co. LLC) and BCM-95 were each administered in a single dose of eight 500-mg capsules, each containing 450 mg total curcuminoids, taken with a glass of water. Blood samples (5 mL each) were taken before (zero hour) and 1, 2, 3, 4, 6, 8, 10, and 12 hours post-dose. The blood samples were extracted with ethyl acetate, concentrated, dissolved in the methanol, and analyzed for the presence of curcuminoids using an HPLC system (column: C18, solvent: isocratic methanol, detection: UV 420 nm). Curcumin was observed in the plasma samples of volunteers after consumption of the Sigma preparation, with a peak plasma concentration of approximately 300 ng/g, a Cmax at four hours post-dose, and complete elimination by six hours post-dose. BCM-95 produced a peak concentration of 1600 ng/g, a Cmax in plasma samples at five hours, and a return to baseline after eight hours. The authors of the study calculated that the bioavailability of curcumin was improved five- to seven-fold with BCM-95; presumably this comparison came from measurements of the AUC.

Another PK study compared the profiles of curcumin (Sigma-Aldrich Co. LLC) to BCM-95 and a mixture of curcumin with lecithin and piperine†† (Life Extension; Fort Lauderdale, Florida).50 The crossover study included 11 healthy adult subjects aged 28-50 years, who refrained from taking aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs) and all foods containing turmeric for two days prior to the study. After an overnight fast, group 1 (n = 4) received four 500-mg capsules of BCM-95 (2 g), group 2 (n = 4) received the same amount of curcumin, and group 3 (n = 3) received the curcumin-lecithin-piperine formula. Blood was drawn immediately prior to dosing and hourly up to six hours and then eight hours post-dose. After a washout period of two weeks, the subjects repeated the protocol taking a different test agent. Group 1 took the standard curcumin and groups 2 and 3 took the BCM-95 product. Blood was tested for the presence of curcuminoids following extraction by ethyl acetate and analyzed via HPLC-UV (column: C18, solvent: isocratic methanol, detection: 420 nm). Peaks were assigned in comparison with a standard reference curcumin preparation from Sigma. Absorption of curcumin from BCM-95 was faster than from standard curcumin, peaking at one hour to give a mean of 316 ng/g, dropping at the second hour to 275 ng/g, and then reaching its highest level of 457 ng/g at 4.5 hours post-dose. Thereafter, plasma levels declined but were still measurable eight hours post-dose. In contrast, standard curcumin produced a peak plasma concentration of approximately 150 ng/g at two hours post-dose and was eliminated by 4.5 hours post-dose. The half-life for BCM-95 was approximately five hours compared to 2.5 hours for standard curcumin. The AUC(0-infinity) was approximately seven times greater for BCM-95 (3200 ng/g/h vs. 460 ng/g/h). In summary, the absorption of BCM-95 was more rapid and resulted in higher plasma levels for a longer period of time compared to standard curcumin.

The mean plasma concentration of curcumin from the curcumin-lecithin-piperine mixture reached a peak plasma level of 344 ng/g at 3.5 hours post-dose. The comparative values for BCM-95 were a peak plasma level of 689 ng/g at 4.7 hours post-dose. The elimination rate constant for curcumin-lecithin-piperine was 0.34/h compared to 0.14/h for BCM-95. The AUC(0-infinity) for BCM-95 was six times higher than that for the curcumin-lecithin-piperine mixture (3975 ng/g/h vs. 624 ng/g/h). Thus, the bioavailability measurements for BCM-95 were also greater than that for the curcumin-lecithin-piperine mixture. The above paper gave separate comparisons for BCM-95 vs. standard curcumin and BCM-95 vs. the curcumin-lecithin-piperine complex, but lacked a direct comparison between standard curcumin and the curcumin-lecithin-piperine complex. The difference between the peak plasma levels of BCM-95 in the two studies (689 ng/g vs. 457 ng/g) suggests differences in the extent of the absorption of BCM-95 or in analyzing of the samples.

A randomized, double-blind, crossover study with 12 healthy volunteers (11 men and one woman) compared the absorption of curcuminoids from four different preparations.51 Absorption from BCM-95 was compared to a phytosome formulation (CP); a combination product containing a hydrophilic carrier, cellulose derivatives, and natural antioxidants (CHC); and standard curcumin (CS). Subjects consumed six optically identical hard gel capsules of each of the products. According to the paper, the amounts of each product were calculated to provide 376 mg of total curcuminoids, with the exception of CS, which provided 1,800 mg total curcuminoids. The exact amounts of each product given in the study and the means of calculating the 376 mg and 1,800 mg were not provided. Each volunteer completed four trials, with blood being collected over 12 hours following intake of each product. The blood samples were centrifuged and frozen before analysis. Before analysis, the samples were treated with a mixture of beta-glucuronidase and sulfatase to hydrolyze the metabolic conjugates to their aglycone forms. The samples were analyzed using HPLC/MS/MS and compared to an internal standard “salbutamol.” Results were obtained individually for curcumin, demethoxycurcumin, bisdemethoxycurcumin, and the metabolite THC. The absorption of total curcuminoids from BCM-95 was only slightly higher than CS (relative absorption 1.3). The relative absorption for CP was 7.9-fold higher than CS, and CHC was 45.9-fold higher than CS. The difference in results for BCM-95 is likely due to differences in methodologies. This method included a hydrolysis step in order to measure both free and conjugated forms in the blood. There is also some ambiguity as to the exact amounts of product administered in the study. Also, there were some differences in the curcuminoid profiles of the products, which were not discussed.