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Infamy, infamy, they’ve all got it in for me! Part 2:

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Not surprisingly, improving the bioavailability has turned out to be the holy grail in the halls of natural product research labs the world over. There are many ways to improve bioavailability, these can range from: incorporating compounds like curcumin into “cage-like” molecules called cyclodextrins, to combining ingredients with powerful polymers (called block polymers), to forming extremely small-size micro or nano-emulsions, to using powerful surfactants like Tween, or by making the curcumin more lipid-soluble by coating it with various phospholipids usually derived from soy. Unfortunately, many of these methods use unapproved ingredients as per regulatory authorities like Health Canada or the FDA. Still others use ingredients that would not be considered food-grade or natural and are thus considered inappropriate.

black-pepper-cornsThen there is the case where some companies use piperine, an alkaloid from black pepper. Black pepper is a widely consumed spice and has been used for centuries by virtually every culture. The rationale for the use of piperine to enhance the bioavailability of curcumin and other ingredients is that piperine inhibits or “knocks-out” the phase 2 enzyme system whose job is to attach various groups like glucuronide or sulphate to any molecule friend or foe that enters the blood. Phase 2 enzymes are a family of enzymes that literally act as the last line of our defence system. Attaching these groups makes molecules more soluble and thus easily excreted through the urine. For friendly molecules like curcumin, or the various flavonoids like quercetin which we get from fruits and vegetables, that’s not good since they are quickly excreted before much benefit can be derived. However, for unfriendly molecules like carcinogens, solvents (from petrol fumes or paints), chemicals or prescriptive drugs, then phase 2 enzymes are really useful. The longer these molecules stay in the body, the greater harm they can cause. So the phase 2 enzyme system is there for a reason and that is to protect us. No wonder this enzyme system is described as the major detoxification pathway. You don’t want to fiddle with it, especially if inhibiting it.

It is strange indeed that no one seems to have raised this alarming concern about inhibiting the phase 2 enzymes, this “gatekeeper”, while possibly allowing the good guys like curcumin to stay in the body but also allowing the “bad” guys like carcinogens to stay as well! The only person to have ever raised this issue is Clark Sayer. Sayer has been a lone voice for well over five years, and surprisingly when this matter is brought up at scientific discussions researchers generally agree with him. Surely then, isn’t it better not to use this ingredient as a bioavailability enhancer until more research actually proves its usefulness and safety? However, quite a few companies continue to use this approach of inhibiting this key detoxification system! Far better to use other approaches like solid lipid particles that not only protect the curcumin from degradation by alkali, bile acids and other digestive enzymes through a protective covering, but that can also be reduced in size so that such particles can easily bypass the enterocytes, the cells lining the small intestines and enter straight into the blood. One such approach has been taken by scientists at the famed University of California in Los Angeles (UCLA). Working in their neuroscience laboratory, Drs Bruce Cole and Sally Frutchey were interested in how curcumin can prevent and/or reverse the sticky plaque that develops in the nerve cells (neurons) of many Alzheimer’s disease patients and decided to look at a non-piperine approach to enhancing bioavailability. After looking at over two hundred formulations, they finally developed the curcumin solid lipid particle as the best candidate to delivering curcumin into the brain. This formulation is called Longvida (see www.longvida.com) and was tested in bone cancer patients in India to see if it was more bioavailable than regular curcumin. Indeed the area under the curve (AUC) which is a measure of bioavailability, was between one hundred to two hundred times that of regular curcumin. The duration of the effect was greatly increased, as the formulation stayed in the system for a longer time since it was protected by the lipid covering. Clinically, the benefits to the patients were reduced episodes of pain, improved quality of life, and significant improvements in the remission rate. While this study was small, nonetheless the results did compare this new delivery system directly with curcumin. The study was repeated in 2012 at the University of Ohio when researchers gave a much smaller dose (80mg) to healthy patients and observed that curcumin was able to get into the brain in high enough concentrations and reduce the plaque formation within just thirty days! Finally, another key feature of this delivery technology over others was that the curcumin delivered to the active site was in the free curcumin form rather than the glucuronide or sulphated form which is typical of other delivery systems. This was discussed in part 1 of the bioavailability issue last time.

In conclusion, while piperine which is derived from the common food ingredient black pepper, the mechanism of inhibiting a defence system like the phase II enzymes to improve bioavailability may not be the best approach to take until more research into the long term effects are studied. Instead it may be a better option to use other technologies like the solid lipid particles that are proven to be safer and deliver higher amounts of active component to the target site.

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