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Curcumin Ultra: A Revolution in Curcumin Delivery

Curcumin is a natural phenol in the turmeric plant (Curcuma longa), a perennial herb belonging to the gin-ger family. Turmeric is commonly used in East Asian curry dishes, and curcumin is responsible for giving these dishes their distinct yellow colour. Curcumin has been used in traditional Ayurvedic medicine to treat joint pain and various types of chron-ic inflammatory conditions. A substantial amount of pre-clinical and human studies have highlighted the health-promoting ef-fects of curcumin, namely its role as an anti-oxidant and anti-inflammatory agent. Over the last decade, there has been an influx of curcumin based natural products on the market. However, biochemical analysis has shown that curcumin is insoluble in water and gastrointestinal fluid. It is rapidly metabolized but poorly absorbed by cells. Curcumin has poor blood brain barrier (BBB) permeability and is rapidly eliminated from the body. All of these facts limit the effectiveness of curcumin as a natural therapeutic agent.

Forms of Curcumin

Curcumin exists in two forms: conjugated and unconjugated (free-form). Various eports have highlighted that conjugated curcumin has low bioavailability and low bioactivity, in contrast to the free-form of curcumin which has high bioavailability and high bioactivity (1-3). Despite this knowledge, consumers have limited options in terms of products that provide high bioavailability/bioactivity free-form curcumin. As such, the unconjugated and less effective form of curcumin continues to flood the market.

Curcumin Ultra is a new product from AOR, which unlike any other product on the market is a unique combination of free-form curcuminoids (CurQfen®) with water-soluble turmeric polysaccharides (Turmacin®). This new, exciting formulation provides the highest levels of bioactive free-form curcumin on the market. Hence, Curcumin Ultra overcomes the limitations that most curcumin products on the market continue to face, i.e. poor bioavailability (see Figure 1).


Figure 1:
Bioavailability of Curcumin UltraPlasma curcumin concentration after supplementation with a single cap-sule of CurQfen®, in comparison to data for a single capsule of other curcumin products (A-G). Data from (7-11)

Highest Boavailability of Curcumin

CurQfen® is a new, enhanced, bioavailable curcumin formulation using fenugreek-derived soluble dietary fibre containing galactomannans. Galactomannans are polysaccharides that have a gum-like character with high viscosity, making it an efficient encapsulation agent. Curcumin forms non-covalent bonds with galactomannans, which make the complexes stable, water dispersible and muco-adhesive. In a double-blind randomised human study of 50 patients, the bioavailability of CurQfen®was compared to standard curcumin (4). Blood samples were collected from patients following a period of fasting for 12 hours. Patients were subsequently administered CurQfen® (free-form curcuminoids) or standard curcumin (control). Blood samples were taken up to 12 hours after administration and plasma concentration of curcuminoids were measured.

The authors found that the plasma concentration of free-form curcumin was higher in patients administered CurQfen®(250 mg or 1000 mg), compared to a similar dose of standard curcumin (based on Cmax and AUC; for an explanation of these terms see Key Terms in margin). To the best of our knowledge, the plasma levels of free-form curcumin in patients administered CurQfen® were the highest concentrations to have been published (2.274 μg/ml.h). This study was also the first to report the ratio of conjugated to free-form curcumin (approximately 1:3), which indicated significant bioavailability of free-form curcumin.

Few studies have investigated the uptake of curcumin and its distribution in cells/tissues throughout an organism. An animal study in which rats were orally administered CurQfen® is the only study to have reported the uptake and distribution of curcumin in animal tissue (2). In this study, male Wistar rats were fasted overnight before being administered CurQfen® (200 mg per kg body weight) or standard curcumin (control). Plasma samples and selected organs were assessed at a range of time-points over 24-hours after administration. Cmax and AUC measurements indicated that the plasma concentration of curcumin was higher (25-fold) in the CurQfen® group compared to the control group, over the 24-hour period. These findings suggested CurQfen® has greater stability in systemic circulation even after passing through the kidneys and the liver. Furthermore, in liver, kidney, heart, spleen, brain, and intestine the concentration of curcumin was higher in the CurQfen® group compared to the control group. The higher level of uptake of curcumin in the CurQfen® group ranged from 12.5-fold (intestine) to 350-fold (brain).

Blood-Brain Barrier Permeability and Neuroprotection

The brain is considered to be a protected organ due to the highly impermeable blood-brain barrier (BBB). The absorption of curcumin into the brain is therefore a significant challenge that few curcumin products overcome. However, results demonstrated that CurQfen® was able to cross the BBB (2). Other preliminary studies have also shown that CurQfen®is neuroprotective in mice that have been administered the endotoxin LPS to induce an acute inflammatory response. In comparison to mice given LPS alone or LPS supplemented with standard curcumin, mice given LPS with CurQfen®showed lower anxiety and better cognition and working memory, suggesting less tissue damage (AKAY Group Ltd, unpublished data).

Fatigue, Anxiety, and Stress

n a recent randomized, double-blind, placebo controlled human study, the safety, antioxidant efficacy and bioavailability of CurQfen® was again compared to standard curcumin (5). A cohort of 60 participants experiencing occupational stress were either administered a placebo or 500 mg of CurQfen® or 500 mg of standard curcumin, twice daily for a period of 30 days. After 30 days of administration, the fatigue, anxiety and stress levels of the participants in each group were measured and compared with the levels measured before administration. The findings showed that fatigue, anxiety and stress levels were most significantly reduced by CurQfen® supplementation when compared with standard curcumin (Figure 2). In contrast, fatigue, anxiety and stress levels were increased (albeit not significantly) in the placebo group at the end of the 30-day period.


Figure 2: Legend
Effect ofCurQfen® on Levels of Fatigue, Anxiety and StressAfter 30 days of supplementa-tion, the fatigue, anxiety, and stress levels of human participants were more significantly reduced with Cur-Qfen® supplemen-tation compared to supplementation with standard cur-cumin. A negative percentage change indicates improve-ment in fatigue, anxiety, and stress levels. Reproduced with permission from (5).

Arterial Stiffness

In another human study (6), the effects of CurQfen® supplementation in young obese men with aortic stiffness were investigated. Aortic stiffness, which was assessed by carotid-femoral pulse wave velocity (cfPWV), is a predictor of cardiovascular events and can be caused by obesity. 22 obese participants (BMI >30 kg/m2) were either administered CurQfen® or placebo. Participants with aortic stiffness had improved cfPWV measurements after 12-weeks of CurQfen®supplementation. This suggested that CurQfen® supplementation had caused a reduction in aortic stiffness. A greater improvement of aortic stiffness was observed in participants with higher cfPWV measurements at baseline (i.e. greater aortic stiffness before supplementation) compared to participants with lower baseline cfPWV (less aortic stiffness before supplementation). Furthermore, levels of IL-13 (an anti-inflammatory cytokine) were significantly reduced after CurQfen®supplementation, which may be one mechanism by which CurQfen® affects obesity-associated aortic stiffness.

Osteoarthritis Symptoms

Despite being water-dispersible, CurQfen®is not water-soluble. However, Curcumin Ultra also contains water-soluble turmeric polysaccharides (Turmacin®), which further improves the bioavailability of free-form curcuminoids (10-fold).

Preliminary human studies in osteoarthritic patients have shown promising results. In a randomized, single-blind, placebo controlled study, the effects of Turmacin®(1000 mg/day) on a variety of clinical parameters over a 42-day period was compared to glucosamine (1500 mg/day), Turmacin® and glucosamine (2500 mg/day), or placebo (800 mg/day) (Natural Remedies Ltd, unpublished data). Osteoarthritis patients given Turmacin®had the greatest symptom improvement (measured by physical performance, questionnaires and clinician assessment). Turmacin® was well-tolerated and no adverse reactions associated with treatment was reported.

Conclusion

Curcumin Ultra contains free-form curcumin (CurQfen®) in combination with water-soluble turmeric polysaccharides (Turmacin®) for enhanced bioavailability and bioactivity (4). Human studies have found that supplementation with CurQfen®may reduce levels of fatigue, anxiety, and stress (5) and improve aortic stiffness (6). Animal studies have suggested that the distributed of CurQfen® to the liver, kidney, heart, spleen, brain, and intestine is greater than standard curcumin (2), and that CurQfen® may have neuroprotective properties, while Turmacin® may have anti-osteoarthritic properties (Natural Remedies Ltd, unpublished data). The unique combination of CurQfen® and Turmacin® makes Curcumin Ultra a ground-breaking curcumin formulation delivering bioactive free-form curcumin for relief of neurological, cardiovascular and osteoarthritic symptoms.

References

1. Ji et al. Can improving the bioavailability improve the bioactivity of curcumin. Trends in Pharmacological Sciences. 2014;35:265-266.

2. Krishnakumar et al. Improved blood-brain barrier permeability and tissue distribution following the oral administration of a food-grade formulation of curcumin with fenugreek fibre. Journal of Functional Foods. 2015;14:215-225.

3. Sandur et al. Curcumin, demethoxycurcumin, bisdemothoxycurcumin, tetrahydrocurcumin, and turmerones differentially regulate anti-inflammatory and anti-proliferative responses through a ROS independent mechanism. Carcinogenesis. 2007;28:1765-1773.

4. Kumar et al. Enhanced bioavailability and relative distribution of free (unconjugated) curcuminoids following the oral administration of a food-grade formulation with fenugreek dietary fibre: a randomised double-blind crossover study. Journal of Functional Foods. 2016;22:578-587.

5. Sudheeran et al. Safety, tolerance, and enhanced efficacy of a bioavailable formulation of curcumin with fenugreek dietary fiber on occupational stress: a randomized, double-blind, placebo-controlled pilot study. Journal of Clinical Psychopharmacology. 2016;36(3):236-43.

6. Campbell et al. Responsiveness to curcumin intervention is associated with reduced aortic stiffness in young, obese men with higher initial stiffness. Journal of Functional Foods. 2016;29:154-160.

7. Cuomo et al. Comparative absorption of a standardized curcuminoid mixture and its lecithin formulation. J. Nat. Prod. 2011;74:664-669.

8. Jager et al. Comparative absorption of curcumin formulations. Nutrition Journal. 2014;13:11.

9. Saski et al. Innovative preparation of curcumin for improved oral bioavailability. Biol. Pharm. 2011;34(5):660-665.

10. Kanai et al. Dose escalation and pharmacokinetic study of nanoparticlecurcumin, a potential anticancer agent with improved bioavailability, in healthy human volunteers. Cancer Chemother. Pharmacol. 2012;69:65-70.

11. Gota et al. Safety and pharmacokinetics of a solid lipid curcumin particle formulation in osteosarcoma patients and healthy volunteers. J. Agric. Food. Chem. 2010;58:2095-2099.

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