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Curcumin Buy Online !!EXCLUSIVE!!

A study published in BMC suggests that curcumin, a naturally occurring substance found in a common spice, might help ease osteoarthritis pain. In the study, researchers enrolled 139 people with symptoms of knee osteoarthritis. Their symptoms were at least moderately severe and required treatment with a nonsteroidal anti-inflammatory drug (NSAID). For one month, they were given the NSAID diclofenac (50 mg, twice daily) or curcumin (500 mg, three times daily).

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Moreover, secondary biliary metabolism was dihydro-ferulic acid and ferulic acid [2,14]. Phase II metabolism is quite active, in the intestinal and hepatic cytosol, on both curcumin and its phase I metabolites especially by conjugation with glucuronic acid and sulfate at the phenolic site. Curcumin is sulfated by SULTs in the cytosol, mainly SULT1A1 and SULT1A3, whereas UGTs catalyse the glucuronidation of curcumin in the intestinal and hepatic microsomes. Dihydrocurcumin, tetrahydrocurcumin, and hexa-hydrocurcumin exist in both free-forms or as glucuronides [2,6,14,16].

Healthy volunteers (n = 24) were administered with a single dose of curcumin standardized powder extract with doses ranging from 0.5 to 12 g. The dose was followed by a cup of water and a standard meal containing dietary fat. No curcumin was detected in the serum of participants administered with a dose inferior to 8 g. In 2/24 subjects, curcumin was found at a level of about 30 (1 h), 40 (2 h), and 50 (4 h) ng/mL after a dose of 10 g whereas level of about 30 (1 h), 60 (2 h), and 50 (4 h) ng/mL after a dose of 12 g [26].

Another study in human volunteers (n = 4) was undertaken to investigate the pharmacokinetics of curcumin taken in turmeric-containing food: a sandwich made from turmeric-containing bread and a portion of soup, plus a sweet oat bar. Each subject consumed 3 g turmeric in total (approx. 100 mg of curcumin). Curcumin was investigated in plasma and detected in only 1/4 volunteers with a Cmax of 3.2 nM at 2 h post-food ingestion. Significant metabolites of curcumin including curcumin glucuronide, demethoxycurcumin glucuronide, and curcumin sulfate were detected in all four volunteers with a Cmax 47.6 28.5 nM, Cmax 1.9 1.2 nM, and Cmax 2.1 1.7 nM respectively. These concentrations were achieved at 30 min post-food [32].

The viability of oral curcumin was also evaluated in gemcitabine-resistant patients with pancreatic cancer (n = 21) who received 8 g oral curcumin daily in combination with chemotherapy. Curcumin pharmacology was studied in n = 5 patients heterogeneous in terms of duration of curcumin treatment and time of blood draw after final curcumin intake. Total curcumin levels (comprehensive of phase II metabolites) ranged from 29 to 91 ng/mL, except for one patient who demonstrated a plasma curcumin level of 412 ng/mL (3 months of curcumin intake, curcumin titration was done 4 h after the final dose). This high plasma level was probably due to a decreased clearance of curcumin caused by constipation related to peritonitis carcinomatosa [33].

Chinese patients (n = 34) who present a decline in memory and cognitive function underwent six months of treatments with curcumin (1 g or 4 g daily). The maximum concentration in total curcuminoids was 92 29 ng/mL [35].

The tolerability and efficacy in Alzheimer disease were also evaluated in patients (n = 36) who receive placebo, 2 grams/day, or 4 grams/day of oral curcumin for 24 weeks. The plasma levels of native curcumin and glucuronide were about seven ng/mL and 96 26 ng/mL, respectively [36].

Levels of curcuminoids were quantified in colorectal mucosa of patients (n = 24) undergoing colorectal endoscopy or surgical resection. Fourteen days before endoscopic biopsy or colonic resection 2.35 g curcumin was administered. Curcuminoids were detectable in plasma samples (9/24), urine (24/24), and the colonic mucosa (23/24). Plasma levels of parent curcumin were 12.2 ng/mL and glucuronides 4.9 ng/mL. Tissue biopsies presented 48.4 mg/g (127.8 nmol/g) of curcumin which was demonstrated to persist in the mucosa for up to 40 h post-administration. In colorectal mucosa, samples were also detected curcumin metabolites and the other curcuminoids (demethoxycurcumin, bis-demethoxycurcumin).

A crossover study was carried out in healthy volunteers (n = 9) to measure plasma concentrations of curcuminoids after supplementation with two dosages of formulated curcuminoids mixture with lecithin (200 or 400 mg/day) and one dosage of non-formulated curcuminoid mixture (about 2 g/day). No plasma peak of free curcumin was detected in any plasma samples. After enzymatic hydrolysis, the concentrations of total curcuminoid were: (1) 206.9 164.7 ng/mL at 2.7 1 h after the administration of 400 mg of formulated preparation, (2) 68.9 50.8 ng/mL at 3.3 1 h after the administration of 200 mg of formulated preparation, and (3) 14.4 12.5 ng/mL at 6.9 6.7 h after the administration of non-formulated curcuminoid mixture. In respect of only curcumin, the concentrations (ng/mL) were 50.3 12.7 at 3.8 0.6 h (400 mg of formulated preparation), 24.2 5.9 at 4.2 0.8 h (200 mg of formulated preparation), and 9.0 2.8 at 6.9 2.2 h (crude curcumin powder) respectively. The phospholipids formulation with lecithin increased the bioavailability of curcuminoids [45].

In rats, peak plasma concentration and AUC were 5-fold higher for Meriva (a combination of curcumin-phospholipids) than for unbound curcumin [57]. Another small single-dose study demonstrated a comparable absorption of curcumin from 450 mg of Meriva and 4 g unbound of Curcuma longa [58].

A water-soluble curcumin formulation containing turmeric extract, a hydrophilic carrier (polyvinyl pyrrolidone), cellulosic derivatives, and natural antioxidants (tocopherol and ascorbyl palmitate) was compared to standard curcumin in healthy volunteers. This novel formulation with an increased solubility provided a 46-fold increase in oral absorption as compared with the unformulated curcumin [48].

Liposomes are molecular assemblies like micro or nanospheres where lipids are organized in one or more bilayers surrounding an aqueous environment. They can be loaded with both hydrophilic and hydrophobic molecule, and to improve their stability they can be coated with polymers. In this, in vitro study, the bioavailability of curcumin was investigated in chitosan-coated liposomes containing curcumin as well as in loaded anionic liposomes. These two loading systems provided the same percentage of curcumin for absorption (bioaccessibility), but chitosan-coated liposomes delivered a higher concentration of bioactive curcumin (transformation). The results were a higher amount of curcumin in the bile salt micelles for curcumin loaded into chitosan-coated liposomes which displayed, indeed, a better bioavailability [15].

Amorphous ternary nano complex of curcumin-chitosan-hypromellose exhibited superior (1) physical stability after 12-month storage, (2) dissolution characteristics, (3) solubility enhancement in simulated gastrointestinal fluids, and (4) minimal cytotoxicity towards human gastric epithelial cells. This nanocarrier may be promising to enhance curcumin solubility and thus its bioavailability [63].

Issues which greatly limit the effectiveness and usefulness of curcumin are its low bioavailability attributed to water insolubility, and rapid metabolism to inactive metabolites. Curcumin is an oil-soluble compound, practically insoluble at room temperature in water at acidic and neutral pH. While it is soluble in alkali, it is very susceptible to auto-degradation. The water solubility of curcumin is estimated to be 11 ng/mL ( ). Therefore, various formulations have been developed to enhance solubility or dispersibility with the goal of enhancing bioavailability and consequent bio-efficacy [14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37]. The reported delivery systems for curcumin include micelles, liposomes, phospholipid complexes, microemulsions, nano-emulsions, emulsions, solid lipid nanoparticles, nanostructured lipid carriers, biopolymer nanoparticles and microgels. They not only enhance efficacy [14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42], but also increase curcumin bioavailability by optimal permeation in the small intestine and preventing possible degradation in the gastrointestinal tract [43].

These formulation strategies are summarized in Table 1. In addition, the Table provides information on whether human pharmacokinetic studies have been published involving the various formulations, and whether enzymatic hydrolysis of plasma samples prior to extraction and analysis of curcumin were employed. Additional information regarding pharmacokinetic studies and enzymatic hydrolysis are provided below.

In addition to the above commercial formulations, a wide range of micellar and nano-particle formulations of curcumin have been prepared involving the use of ingredients as Tween 80, polysorbate 80, ceramic particles, polyethylene glycol (PEG), alginate, poly(lactic-co-glycolic acid) (PLGA), omega-3 fatty acids, chitosan and other substances [38,39,40,41,42]. Chemically modified variations of curcumin as well as conjugates in addition to the above formulations have been also developed. However, no pharmacokinetic studies have been reported to demonstrate the improvement in absorption and bioavailability [38,39,40,41,42]. As a consequence, only limited claims for greater bioavailability and efficacy can be justifiably made. Furthermore, it is not clear whether all of the ingredients used in these diverse formulations have generally recognized as safe (GRAS) status and can therefore be used in human subjects.

Delivery systems as micelles, liposomes, phospholipid complexes, microemulsions, nano-emulsions, emulsions, solid lipid nanoparticles, nanostructured lipid carriers, biopolymer nanoparticles and microgels exhibit greatest promise. They enhance efficacy [38,39,40,41,42], and also increase curcumin bioavailability by enhancing small intestine permeation, preventing possible degradation in the microenvironment, increasing plasma half-life and enhancing curcumin efficacy [43]. 041b061a72


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