Why Free Curcumin is the Only Curcumin that Matters

Published on July 05, 2015 by Dr. Traj Nibber

When you swallow any natural health product(NHP) like an herb, vitamin or any other supplement in a capsule or tablet, you expect that the product gets into the blood and reaches the target site, whether it is a sore knee, an inflamed ankle or the sluggish liver you are trying to invigorate.

Bioavailability is a fancy pharmaceutical term that describes how much of an active ingredient is absorbed into the blood by the body and remains unchanged before it reaches its target destination. High bioavailability is the ultimate goal for any pharmaceutical or NHP as it promises better efficacy. Unfortunately, it is estimated that over 40% of all new pharmaceutical drugs, even though they show considerable early promise, are abandoned because of poor bioavailability.

Bioavailability is a huge problem in the pharmaceutical world and in the natural health world. It’s a common fallacy to think that just because one is taking a natural product, it will get absorbed into the blood intact. Once ingested, most ingredients are changed (metabolized) by the body before they are absorbed into the blood and reach their destination. This metabolism often renders the active ingredients as less effective. Quercetin, Green Tea, and especially curcumin, the yellow pigment found in the turmeric root and widely used in Asian cuisine, all have poor bioavailability (anywhere between 1-10%).

If the product you are taking isn’t getting into the blood intact, then what is the point of a rigorous supplement regimen?

Bioavailability is dependent on a number of factors, including:
• Solubility- The active ingredient must dissolve into the contents of the stomach. Very little is going to get absorbed if it isn’t soluble (think sand mixed with water).
• Stability- The ingredient must not be destroyed by the contents of the gut. Surviving harsh acidic or alkali conditions, various enzymes and, bile acids is very important.
• Permeability- The active ingredient must get across the cells of the stomach or intestines and into the blood.
• Metabolism- the active ingredient must resist break down by enzymes present in the lining of the gut, and to a greater extent in the liver, where compounds that are not in their original form are broken down.   

The challenge for any formulation scientist is to overcome these issues. Let us take curcumin, my favourite molecule and perhaps the most widely studied natural health product on the planet, as an example. There are thousands of researchers all over the world working on this fascinating molecule for its wide variety of proposed health benefits, such as reduction of cholesterol, protecting against diabetes, promoting liver health, its numerous anti-cancer activities to inflammation, heart health and many other effects. Unfortunately, curcumin has one big drawback and that is its poor bioavailability which necessitates very large doses in NHPs (sometimes up to 10 grams).   
If the bioavailability of curcumin could be improved, you would have a natural product that could compete with any pharmaceutical!

There are many strategies for improving bioavailability including making micelles (little fat globules) with phospholipids, reducing particle size to nanometer range or adding inhibitors of metabolic enzymes and so on. This has lead companies to report bioavailability increases anywhere from 7-27 fold compared to the regular curcumin supplement. In fact, the bioavailability war is heating up which has led to misleading and false claims (one brand even claims to have ten times the bioavailability that its own scientist reported)! Unfortunately, none of the curcumin products on the market have overcome all of the challenges- until recently.

Neuroscientists at UCLA in Los Angeles tested many products on the market in North America and Europe but were disappointed to find that none of these products resulted in measurable levels of unchanged or free curcumin in the blood as well as the brain. So they decided to develop their own formula that would address all the challenges.
After testing over two hundred different formulations, they developed a curcumin solid lipid particle (C-SLP) that overcame all the hurdles and yielded a high bioavailability and clinically effective curcumin. This formula was patented and is licensed under the trade name Longvida, a unique and highly optimized form of free curcumin.

The key to the Longvida optimized curcumin delivery system is the following:

• Small particle size of curcumin so it can easily cross the intestinal cells into the blood. The larger sized molecules cannot get past the radar of the ever watchful gatekeeper stationed at the cell 1membrane.
Longvida curcumin is able to survive the harsh digestive pH conditions, unlike most other forms of curcumin and doesn’t get destroyed by the acidic environment of the stomach.
• The unique coatings around the curcumin molecule, made up of highly purified fatty acids and phospholipids in a very specific ratio, enable it to be transported into the lymphatic system rather than the circulatory system. This is very important because unlike the circulatory system, the lymphatic system bypasses the liver (the major organ for metabolism) so less curcumin is exposed to metabolic enzymes and remains in a free form. The sole purpose of these metabolic enzymes is to attach large groups (called glucuronides or sulphates) to the curcumin molecule, making it very bulky but also highly water soluble so it can be rapidly excreted by the kidneys and out of the body in urine. On the other hand, the free form of curcumin stays in the body longer because it isn’t metabolised and doesn’t have these water soluble groups attached to it so, it has a longer duration of action which is another important feature of Longvida form of curcumin.

This makes sense because the purpose of the metabolic enzymes is to protect the body by attaching such groups to make them more soluble and thus rapidly excrete them out of the body. Anything that interferes with this process, such as piperine, a compound found in black pepper and used by some companies to improve bioavailability, may pose a health risk. How so? Piperine knocks out the gate keeper (the protective metabolic enzymes) and thus allows both the ‘good guys’ (curcumin) as well as the ‘bad guys’ (toxins or carcinogens) into the blood stream.

An important point to be made is that the metabolized form of curcumin, also known as a glucuronide or a metabolite, is not the same as curcumin that isn’t metabolized by the body (free curcumin). It’s mistakenly thought that the metabolite has similar health properties to the free curcumin as portrayed by some companies, but research suggests otherwise (Prasad et-al, 2014).

The metabolite is at best less active. In other cases, the metabolite is also less powerful as an antioxidant or anti-inflammatory. In addition, the glucuronide curcumin is unable to get across the cell membrane as reported by Shoji et-al (2014). So clearly, it is important to get as much of the original un-metabolized form or free curcumin in the blood as possible.

One major flaw in experimental research on curcumin is the testing methodology as reported in the majority of published papers. One can learn a lot about how the materials are handled and measured in the materials and method section of a scientific paper. Supplement companies “cheat” by using some fancy testing process and declaring their blood levels of metabolized curcumin as being the same as free curcumin. 

Free Curcumin vs. Glucuronadated Curcumin

When measuring blood levels, most companies take the metabolite and not a free curcumin and subject it to treatment by a bacterial/animal derived enzyme called glucuronidase, which breaks up the bond between the glucuronide group and curcumin and thus falsely claim their blood levels to be equivalent to free curcumin! This smoke and mirror stuff hides what really is being measured, which is the metabolite and not free curcumin!
In fact, in 2012, Professor Andreas Gescher of University of Leicester, one of the leading experts in evaluation of curcumin in humans wrote a scathing response to a recent study that used this method prior to testing free curcumin. Gescher states: “Based on current evidence, parent curcumin – rather than its metabolites – is thought to mediate the anti-carcinogenic properties of this agent. Therefore, the claims made in this paper that theracurmin achieves “….improved bioavailability in human subjects...as compared to that observed after unformulated curcumin is unsubstantiated".

One spokesperson from a different company argues that the testing methodology for Longvida is also not measuring free curcumin because the use of methanol acts like the glucuronidase enzyme and therefore is not measuring free curcumin since methanol was required to produce the free form. However, such a claim is incorrect as methanol does NOT act in a similar manner as the glucuronidase enzyme. It is a different form of methanol that does this and even then, nowhere as effectively as the glucuronidase enzyme! Clearly, people making such claims haven’t done their research.

Because of its small size, a free form molecule like Longvida curcumin can easily get into a cell. The question however remains, how do the metabolized forms get into the cell? Well they have difficulty due their large size so they aren’t going to be as efficiently taken up as the free form. Some companies however argue that the metabolite is acted upon by the enzyme glucuronidase which releases the free form of curcumin, which can then enter the cell. These companies suggest that the enzyme glucuronidase is naturally present in the cell and “leaks” out of the cell thereby acting on the curcumin metabolite waiting on the outside of the cell.

There are two major problems with this hypothesis. First, the enzyme is present in the cell in a separate compartment called lysosomes where the pH is around 4. The pH outside the cell, where presumably the metabolite is waiting to enter, is around 7.2 (typical pH of the blood). Much like today’s superstar athletes, enzymes are fussy prima donnas that require every detail to be perfect before they can perform their functions. Temperature, ionic concentration and most importantly the pH have to be tightly controlled, otherwise enzymes perform their jobs poorly. Difference of 3 in pH is very significant and will reduce the activity of the enzyme by 90% (de Graaf et-al, 2002).

It is true that in some cancers (prostate, breast, colon etc.) the pH of the blood is much lower (due to lactic acidosis) than the typical 7.4 found in healthy individuals. In this case, the “leaked” glucuronidase enzyme may be able to perform effectively. However, what about other conditions such as inflammation, protein glycation or where there is excessive free radical damage? There isn’t evidence that the pH of the blood is around 4. Moreover, typically healthy cells do not “leak” important enzymes.

Even more importantly, many supplement users are healthy and take supplements to maintain their health. In such cases, there is no evidence that the pH is low. To assume that the enzyme will “leak” out of the cell in healthy as well as in varied disease conditions and still be able to break the curcumin glucuronide bond to release the free curcumin is presumptive at best!

The second problem with the “leak” hypothesis is that because the curcumin metabolite is water soluble, the body will do its best to get rid of it via the kidneys. This means that the amount of curcumin metabolite will continually get lower and only small amounts will be available to be acted on by the glucuronidase enzyme. Because the free form curcumin is less water soluble, it will generally be present longer in the body. Having a quicker and longer duration of action is precisely what Longvida form of curcumin achieves.

Curcumin is a versatile and powerful molecule but it is unfortunate that some companies are resorting to misinformation; by claiming that a metabolite is the same as free form curcumin, and by making unsubstantiated claims about huge increases (ten- fold) in the bioavailability of their curcumin.

Still have questions? Let us know in the comment section below or share with us your experience with Curcumin!

Images by © 2013 Piccia Neri and © 2008 Jonathan Ross via DollarPhotoClub


de Graaf M et-al, “Beta Glucuronidase-mediated drug release” Current Pharmaceutical Design, 2002, 8, 1391-1403
Shoji M et-al “Comparison of the effects of curcumin and curcumin glucuronide in human hepatocellular carcinoma HepG2 cells” Food Chemistry 2014, 151, 126-132

Vareed, S K et-al “Pharmacokinetics of curcumin conjugate metabolites in healthy human subjects”. Cancer Epidemiology, Biomarker & Prevention 2008, 17, 1411-1417
Sharma R A et-al “Curcumin: The story so far” European Journal of Cancer, 2005, 41, 1955-1968
Sasaki H et-al, “Innovative Preparation of Curcumin for Improved Oral Bioavailability”. Biol. Pharm. Bull. 2011, 34(5), 660—665
Gota V S 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
Gescher A J, “Dose escalation and pharmacokinetic study of nanoparticle curcumin… by Kanai et al.”
Cancer Chemother Pharmacol 2012, 70, 487
Kanai M, “A Phase I Study Investigating the Safety and Pharmacokinetics of Highly Bioavailable Curcumin (Theracurmin®) in Cancer Patients.” Cancer Chemother Pharmacol; 2013, 71, 1521-1530
Yu N et-al, “Screening of Anabolic Steroids in Horse Urine by Liquid Chromatography-Tandem Mass Spectrometry.” Journal of Pharmaceutical and Biomedical Analysis; 2005, 37, 1031-1038.
Prasad S et-al, “Recent Developments in Delivery, Bioavailability, Absorption and Metabolism of Curcumin: the Golden Pigment from Golden Spice”. Cancer Res Treat. 2014, 46(1), 2-18

  • Kathleen

    How can I tell from a label if I am buying Free Curcumin?

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    • Traj Nibber

      Hi Kathleen, good question.
      There isn't any way you can tell this free curcumin unless the company claims it is free curcumin on their label or their literature. As far as I know all the products are metabolized by the intestinal and liver enzymes and produce curcumin metabolites (like sulphates and glucuronides) and these circulate in the blood stream. These are NOT free curcumin forms. Longvida has the unique distinction of producing high amounts of free curcumin (not metabolized). This is the basis of Longvida's patent licensed from UCLA.

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  • Billy Ezel

    Good blog article.
    Now can I achieve the same results by putting turmeric in butter with some veggies, and some ground pepper

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    • Traj Nibber

      Hi Billy, thanks for commenting. Actually, turmeric is what has traditionally been used in the Ayurveda system for thousands of years not curcumin or the curcuminoids. Typically, turmeric is generally heated in gee or clarified butter and all sorts of spices are added and this base is then added to all the vegetable dishes and/or curries prepared traditionally in India. So your suggestion has strong merit as supported by thousands of years of usage. The use of free curcumin is based on recent scientific data (over say the last 40 years or so) and thousands and thousands of animal and hundreds of human studies that demonstrate that curcumin and curcuminoids are far more active than turmeric alone. Moreover, free curcumin (that does not get metabolized has even more activity). The use of piperine is curious. While black pepper is widely used in various cuisines, piperine's mechanism of action is somewhat controversial as pointed out in the article. Piperine inhibits the metabolizing enzymes and thus raises percentage of free curcumin in the system. However, these metabolizing enzymes are body's defense mechanism protecting unwanted toxic insults e.g. carcinogens, various toxins like environmental- solvents, paints, cigarette smoke, nitrosamines in foods etc. So the question arises is it wise to knock out the gate keeper?

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      • Bob

        Hello Dr. Traj Nibber, I noticed that when people eat powdered or cooked broccoli that there is an enzyme present in the broccoli that makes NAD I believe more bio available. Mustard seeds have the enzyme in them and eating mustard seeds with the powdered broccoli make NAD bio availability I'm beginning to think that simply food processing whole raw turmeric with a little oil or avocado would do the trick. I suspect that the whole food has what it takes to make everything properly digested. Just like other foods. And even if it's not quite as effective, I won't go poor trying anyway. What do you think?

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        • Bob

          Sorry, I meant that powdered or cooked broccoli does not have the enzyme or it is deactivated. Probably because it was not meant to eat it that way.

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        • Traj Nibber

          Broccoli and the whole mustard family is loaded with compounds called glucoraphanins which get converted into the more active sulforaphane which is considered an excellent NrF2 activator (considered a master switch to antioxidant protective system in the body). The enzyme required is myrosinase which is also naturally present in the broccoli.

          Research has shown that broccoli sprouts are an excellent source of the above but the seeds have even higher concentrations (50 times more than sprouts!).
          Your suggestion that these ingredients in broccoli will make NAD more bioavailable makes sense because sulforaphane will prevent NAD getting oxidized and thus present in a more active state- NAD.

          Thank you

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  • Rodney Wagner

    Where can I buy free curcumin ? Is it expensive?

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    • Traj Nibber

      Hi Rodney, the only brand that delivers large amount of "free" un-metabolized form of curcumin is under the brand name Longvida which is sold under the following brand names: <a href="http://aor.ca/en/product/curcuviva" target="_blank" rel="nofollow">CurcuViva</a>, <a href="http://aor.ca/en/product/curcumin-active" target="_blank" rel="nofollow">Curcumin Active</a>, <a href="http://aor.ca/en/product/curculight" target="_blank" rel="nofollow">Curcu Light</a>, <a href="http://aor.ca/en/product/curcumind" target="_blank" rel="nofollow">Curcu Mind</a> by AOR and most retailers carry these brands.

      To find a retailer near you please visit: http://aor.ca/en/find-a-retailer

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  • Yohanan Bar Tanhum

    were i can get the curcum coated with phospholipid manufacturers

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    • Traj Nibber

      Longvida is the brand name and has ten human studies on its clinical effectiveness. This product is sold in Canada under the following names: Curcumin Active (133mg for high level inflammation), Curcu Viva (80mg for cognition) and Curcu Mind (a combination of curcumin 133mg and Vitamin D3 1,000 iu for general cognitive health). Thank you.

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  • Bev

    Please explain the difference between Longvida RD and Longvida SD. How will I know which products are RD or SD as some products only state Longvida? Thank you.

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    • Traj Nibber

      There is no difference between RD and SD. The material is identical, one is for beverages and the other for capsules and tablets. Thank you

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  • Ross

    There is some published preclinical work in mice that suggests curcumin may have some type of negative effect on the P53 gene which is one of the most important defenses against tumorigenesis in humans. Is there any reason to be concerned that curcumin may indeed be carcinogenic as a result of this inhibition of p53? Is there any data to suggest the Longvida formulation might be be able to evade this effect on P53?

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    • Traj Nibber

      There is sufficient evidence that curcumin increases P53 activity and has a strong chemopreventive effect. Longvida has not been studied specifically for P53 gene activity but as mentioned curcumin's anti-cancer effects are thought to be due to numerous mechanisms.

      Thank you

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  • Vikram Naharwar

    It continues to surprise me how little people know about natural products and how far the industry goes to cheat consumers. Am glad there are people like Dr Nibber that stands for the truth .

    Even more alarmingly nearly every company has been pushing bio availability as the cause celebre, without even the slight worry that all they are peddling is nonsense. Water is completely bio available, yet is limited to hydration. It's time consumers get to know the truth before Big Brother is given no choice but to step in and then it's adios to the industry.

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    • Traj Nibber

      Thank you for your comments. AOR will be introducing a sublingual form soon which will also deliver free-form curcumin that delivers the bioactivity rapidly.

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  • Jake Gibson

    Thanks for sharing informative content and best natural health blogs. I would also like to share my website Communitynaturalfoods.com

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  • Chango

    Hello DR Nibber, I am interested in buying some of your AOR longvida, it is really the only brand I found that contains longvida other than NOW Foods in America.

    I have a question, which one of your Longvida product is good for colon health for people with digestive issue like reducing inflammation over all is do I have to use Turmeric for that?

    Do you also ship to USA or have any online retailers in the states that sell your products thanks.

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    • NavNirat Nibber

      Thank you for your comment. Indeed we do sell our products in the USA- you can check out our website www.aorhealth.com for the full list of retailers. As for specific colonic benefits from turmeric. A number of clinical studies have shown benefits of turmeric root in a number of different forms- most recently is the free-form curcumin infused in fenugreek fibre form known as CurQfen.

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