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Meriva^® Bioavailable curcumin

Meriva^® is a patented formulation of curcumin, a dietary phenolic, with soy lecithin⁽¹⁾. The two compounds form a non-covalent adduct in a 1:2 weight ratio, and two parts of microcrystalline cellulose are then added to improve formulation, with an overall contents of curcumin of 20%.
Turmeric has a long history of medicinal use, especially to treat inflammation⁽²⁾,  and many of its traditional uses have been mechanistically validated in cellular systems as well as in animal models of disease. Indeed, with almost 3000 pre-clinical investigations, curcumin is one of the best investigated products of the whole biomedical literature⁽²⁾. These studies have demonstrated that curcumin acts as a master switch of inflammation by acting at level of enzymes (COXs and LOs) and transcription factors (NF-kB) level, as well as at their genomic expression⁽³⁾. However, little clinical evidence of efficacy has so far been reported, and most of the beneficial effects of curcumin are suggested by epidemiological studies, supported by studies in animal models, extrapolated from studies in vitro, but not validated clinically⁽²⁾. This paradoxical situation is mainly due to the poor druggability of curcumin with a dismally low oral absorption, characterized by plasma concentrations that are barely overcome 50 ng/mL after administration of dosages as high as 12 g/die⁽⁴⁾. 

Curcumin, just like most dietary phenolics, is sparingly soluble both in water and in oily solvents, but shows polar groups (two phenolic hydroxyl and one enolic hydroxyl) that can interact via hydrogen bondings and polar interactions with complementary group, like the polar heads of phospholipids. Thus, phosphatidylcholine has a highly polarized head, with the negative charge of a phosphate group and the positive charge of the choline ammonium group, and can complex a variety of poorly soluble phenolics, including curcumin(1).  By embedding curcumin into the environment of phospholipids, curcumin is shielded from water-triggered degradation while, at the same time, the rapid exchange of phospholipids between biological membranes and the extracellular fluids can shuttle it into biological membranes, boosting its cellular captation.

A 2007 study published in the journal Cancer Chemotherapy and Pharmacology⁽⁵⁾ demonstrated Meriva^®'s superior bioavailability compared to a standardized curcumin extract in rats.
Meriva^® improved plasma Cmax and AUC of curcuminoids by 20-fold and levels of curcumin in the liver increased by much more then a 20 folds.

A high oral load of unformulated curcumin (340 mg/Kg) and an amount of Meriva® of 1.8 g/Kg, (corresponding to 340 mg/Kg of curcumin), were administered by oral gavage to Male Wistar rats. The presence of curcumin and metabolites was evaluated at 15, 30 ,60 and 120 minutes after administration in plasma, liver and intestinal mucosa. In accordance with previous studies, 99% of curcumin was present in plasma as glucuronides, with the remaining 1% being curcumin sulphate and free curcumin. Complexation with phospholipids led to a marked increase in the concentration of all the plasma curcuminoids (over 23 fold in the case of glucuronides, ca 5-fold in the case of free curcumin, and ca 1.5-fold in the case of sulphates). Since glucuronides are by far the prevailing plasma curcuminoids, the overall bioavailability of curcumin, as expressed in plasma curcuminoids and calculated from AUC values, was improved by over 23-fold when this compound was administered as Meriva® compared to the unformulated natural product.

In a new comparative study in humans⁽⁶⁾, the overall curcuminoid absorption was about 29-fold higher for Meriva^® compared to the unformulated curcuminoid mixture, while a 50 to 60 fold higher absorption has been shown for demethoxycurcumin and bisdemethoxycurcumin. The improved absorption, and possibly also a better plasma curcuminoid profile, might underlie the clinical efficacy of  Meriva^® at doses significantly lower than unformulated curcuminoid mixtures.

* Normalized AUCs, expressed in ng/mL(plasma) x h/mg ingested, were devided by the AUC of the reference to calculate the relative absorption values.

In a recent registry study⁽⁷⁾, 50 patients with osteoarthritis (OA) divided into two groups were treated with Meriva^®:
Group A was managed using the “best available treatment as defined by patient’s GP and by specialist
Group B was managed using the best treatment as above in association with Meriva administered as a food supplement at a dosage of 200mg curcumin/die, a dosage much lower than those used in previous and ongoing clinical studies, that can reach 8g/die.
Both objective and subjective end-points were evaluated: mobility was studied by walking performance (treadmill), and the inflammatory status was assessed by measurements of C-reactive protein (CRP) plasma concentration. OA signs/symptoms were evaluated by the WOMAC scores.
After three months of treatment, the global WOMAC score (used to evaluate OA signs/symptoms) decreased by 58% (p < 0.05), walking distance in the treadmill test was prolonged from 76 m to 332 m (p < 0.05), and CRP levels decreased from 168 ± 18 to 11.3 ±. 4.1 mg/L in the subpopulation with high CRP. In comparison, the control group experienced only a modest improvement in these parameters (2% in the WOMAC score, from 82 m to 129 m in the treadmill test, and from 175 ± 12.3 to 112 ± 22.2 mg/L in the CRP plasma concentration), while the treatment costs (use of anti-inflammatory drugs, treatment and hospitalization) were reduced significantly in the treatment group.

In a further registry study⁽⁸⁾, 100 patients with X-ray confirmed osteoarthritis (OA), were divided in two groups. The first one was managed using the “best available treatment” and the second group used the best available treatment plus Meriva^®, at a dosage corresponding to 200 mg curcumin/day. The results showed that the Meriva^®-treated group had a statistically significant reduction in all primary clinical end-points, the Western Ontario and McMaster Universities (WOMAC) score, the Karnofsky Performance Scale, and the treadmill walking performance test. These results were complemented by the evaluation of a series of inflammatory markers (interleukin [IL]-1b, IL-6, soluble CD40 ligand [sCD40L], soluble vascular cell adhesion molecule (sVCAM)-1, and erythrocyte sedimentation rate [ESR]) that also showed a marked reduction in the Meriva^® treated group, while no significant variation was observed in the “best available treatment” group.

In a trial on 106 patients⁽⁹⁾ affected by chronic anterior uveitis relapsing since at least 2 years was carried out. A 1200 mg/die dosage of Meriva^® was administered (two tablets per day) for at least twelve months, complementing the therapy already in course. 86% of patients in the Meriva^® group enjoyed a subjective improvement of the overall well being after only 4/6 weeks, with a remarkable reduction in relapses number. Also the number of patients affected by uveitis relapses decreased by over 80%. This suggests that the prolonged intake of Meriva^®, in association to standard treatment, is useful in reducing the ocular problems related to chronic inflammation of the ocular surface. These results qualify Meriva^® as a safe ingredient with a strong potential even in poorly vascolarized tissues as the ocular bulb is.

In another registry study⁽¹⁰⁾, 50 diabetic patients were treated with Meriva^® (1g/day) to evaluate a possible reduction of the endothelial damage related to oxidative stress. Patients, whose disease was manageable without insulin and only with oral antidiabetics were divided in two groups. The first one received Meriva^® for 4 weeks while the second group was used as a control. The presence and evolution of diabetic microangiopathy was measured instrumentally (laser doppler flowmetry, pO₂) and observationally (evaluation of edema at the foot), after 4 weeks of treatment, the Meriva^® group showed an amelioration of all the parameters investigated, as well as a general amelioration of the quality of life, as measured by the Karnofsky scale.

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