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What is the Importance of Free-curcumin?

Curcumin is a well-studied herb, and as such there are thousands of different products on retailer’s shelves. Moreover, there are dozens of different brands with serious marketing dollars towards differentiating their brands and, touting their effectiveness.

Curcumin belongs to a group called curcuminoids comprising three slightly different molecules that are extracted from the root or rhizomes of the Curcuma plant. Curcumin comprises over 80% of this group and is the most researched molecule, and therefore, everyone refers to curcumin when they really mean the curcuminoid group. Virtually all the products on the market consist of this curcuminoid group, and not the single curcumin molecule. In this blog we shall use the colloquial term curcumin to refer top this group.

Why is curcumin so popular and respected?

Curcumin has been extensively researched. It is safe even when taken in high does of up to eight to 12 g per day! Studies show that curcumin has wide and numerous health benefits including: anti-inflammatory and antioxidant effects, cancer protective properties (chemoprevention), anti-bacterial, anti-viral and anti-fungal properties, liver and kidney protection, cognitive properties, and having antidepressant, antidiabetic and immune modulating properties to name a few!

However, despite all the above documented effects, curcumin has some serious issues that need to be addressed if one is to enjoy its full health benefits. First, curcumin is unstable to a variety of environmental conditions including light, oxygen, water, various metallic ions and other conditions. Companies need to be aware of, and take precautions to address these issues when formulating their products. 

Second, curcumin when ingested faces a host of other challenges including poor solubility. If it isn’t soluble, it cannot get absorbed by the body. While curcumin is reasonably stable in acidic conditions of the stomach, it is not stable in the alkaline conditions of the small intestines where pH of 7.5 and higher starts degrading curcumin quickly. Furthermore, curcumin must face the dreaded pancreatic enzymes, and bile salts, which are all too eager to destroy any trespassers.

If some curcumin attempts to get absorbed, through the intestinal cells or enterocytes, then it faces being kicked out by the inherent defense system of these cells. This system is called the pg-efflux system. This is one of the main reasons why many cancer-fighting drugs fail because they are readily kicked-out by the cells and prevented from being absorbed.

Finally, if some curcumin manages to overcome all the above obstacles and gets absorbed into the intestinal bloodstream, the blood then has to go through the liver where it is subjected to the liver’s fine net and then even finer netting to prevent any curcumin from entering the blood circulation. A metaphor for the unrelenting defense system of phase I and phase II degrading enzymes the liver has at its disposal which readily modify anything, friend or foe, so the body can get rid of it fast as possible, so nothing lingers in the body.

It seems that the life of a curcumin molecule is not a happy one. And, because of all these challenges, very little curcumin actually gets absorbed into the bloodstream. No wonder the amount of curcumin that reaches the site of action – a sore knee, a sprained foot, or the overworked, fat-loaded liver, is very small indeed. Too small to do us any good. This is the major challenge facing nutraceutical and pharmaceutical companies. How to deliver the effective curcumin payload to the site of action?

Natural health companies have tried different delivery formulations (e.g., making micelles, nano-emulsions, liposomes, solid lipid particles, cyclodextrin cage molecules, and other technologies), unfortunately, many of these require non-food grade excipients, their safety hasn’t been confirmed, or they are unstable as nutraceutical delivery systems. In this regard, natural product companies have used various ingredients including, medium-chain and long-chain phospholipids, various oils, surfactants and emulsifiers, particle size reduction, etc., in order to overcome the above challenges.

A major hurdle for companies is to demonstrate that their formulated curcumin product is absorbed into the circulation, a phenomenon called bioavailability. The area under the curve (AUC), which is the area under the graph of concentration of curcumin level in the plasma versus time, is regarded as the best measure of bioavailability. The higher the AUC, the greater the bioavailability, and by extension, the more effective the product will be. Companies promote this data and use this as a marketing tool to position their product as superior over others.

AUC of 7X, 9X, 29X, 46x, 65X, 94X and 198X, etc. have been reported by different companies. However, closer inspection suggests that companies are not playing on a level playing field when posting their AUC results. This is because of a fundamental error in the methodology utilized in the sampling of plasma levels that involves the use of the enzyme glucuronidase which greatly inflates (by an order of 10-fold or higher) the total curcumin levels. This misleadingly increases a company’s product as being more bioavailable when in fact it isn’t!

Various researchers have highlighted this flaw and, urged against the use of glucuronidase in sampling analysis. Yet majority of published studies still employ this methodology.

Besides falsely increasing the AUC levels, another huge flaw in the use of glucuronidase enzyme methodology is that higher free-curcumin levels are reported. This is because the phase II detoxification enzymes in the liver inevitably metabolizes or adds glucuronide or sulphate groups to substances like curcumin to form conjugates or metabolites so that they are made more water-soluble so they can be excreted out of the body. The glucuronidase enzyme like a fine pair of scissors cuts off the added glucuronide or sulphate groups and reports them as free-form curcumin.

Why are free curcumin levels important?

Because, the free form of curcumin is a much more powerful and active molecule than the conjugated glucuronide or sulphate metabolite! The free form of curcumin is the biologically active molecule, more active as an anti-inflammatory, anticancer, antibacterial or antiviral, antioxidant and with tissue protecting properties, whereas the conjugated forms have little or no activity. What this means is that most curcumin products unfortunately get metabolized and produce little or no free form curcumin levels which is the active form. A consumer may be misled by the high bioavailability figure, thinking he or she is taking a supplement that will give them the biggest bang for their buck in terms of therapeutic activity when in fact they are not!

Literature search shows that currently, only two commercial curcumin products on the market do not utilize this flawed glucuronidase methodology, which produces a significant free form of curcumin. These are Curcumin Active™ (utilizing Longvida® form of curcumin) and Curcumin Ultra (using CurQfen® form of curcumin).

In summary, it is important that consumers are aware that not all curcumin formulations on the market are equal because of differences in testing methodology. Nonetheless, it is important to appreciate the powerful benefits of formulations that deliver meaningful levels of free form of curcumin over the metabolized curcumin delivery systems in order to get optimal health benefits.


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Dr. Traj Nibber, PhD

About The Author

Dr. Traj Nibber is the Director of AOR, he has a degree in Pharmacy, a Masters in Toxicology and a PhD in Pathology. Dr. Nibber founded AOR to clear the misdirection prevalent in the nutraceutical world, and provide people with highly effective, research backed products.

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