Wanted: Turmeric Curcuminoids

Getting Our Curcuminoids
Is Difficult, but Worth It

Medical science struggles to overcome bioavailability
problem to realize turmeric’s myriad health benefits
By Will Block

f you’ve ever tried to feed a baby who didn’t particularly want to be fed, you know something about the problem of bioavailability. Much of the food that was supposed to go into the baby for nourishment probably wound up on the bib, the high chair, and your clothes. Whatever landed on the floor was probably taken care of by the ever helpful family dog, so that part, at least, didn’t go to waste.

A certain amount of waste is, alas, inevitable where nourishment is concerned, because not all the nutrients we (or our dogs) ingest get to their intended destination, namely, the cells of our body’s many different organs and tissues. That is the crux of the bioavailability problem, which happens to be particularly severe for the compounds that give the Indian spice turmeric (Curcuma longa) its myriad health benefits. Turmeric is the major component of most prepared curry powders, and it gives many mustards and other foods their characteristic yellow color. It’s also a treasure trove of potential medicinal value.

A Terrific Testament to Turmeric

A good indication of the extent to which turmeric is taken seriously by medical scientists is the publication in 2007 of a 492-page book, The Molecular Targets and Therapeutic Uses of Curcumin in Health and Disease.1 Its 21 chapters are devoted to a wide array of topics in this domain, which has been the subject of several hundred laboratory and animal studies over the past three decades.* In a recent review article coauthored by the book’s lead editor, the situation was summarized as follows (literature citations omitted):2

Traditionally, turmeric has been used for many ailments, particularly as an anti-inflammatory agent, and curcumin has been identified as the active principle of turmeric. Curcumin has been shown to exhibit antioxidant, anti-inflammatory, antimicrobial, and anticarcinogenic activities. Additionally, the hepato- and nephro-protective [liver- and kidney-protective], thrombosis-suppressing, myocardial infarction-protective, hypoglycemic, and antirheumatic effects of curcumin are also well established. Various animal models or human studies proved that curcumin is extremely safe even at very high doses. . . . Similarly, the efficacy of curcumin in various diseases, including cancer, has been well established. Several clinical studies dealing with the efficacy of curcumin in humans can also be cited. The pharmacological safety and efficacy of curcumin makes it a potential compound for treatment and prevention of a wide variety of human diseases.

That’s quite a testament! As indicated in the quote, curcumin, a polyphenolic compound, is the principal active ingredient in turmeric; it shares its therapeutic role with two closely related compounds called curcuminoids: demethoxycurcumin and bis(demethoxy)curcumin. In the context of medicine or nutrition, either of the terms curcumin or curcuminoids is usually understood to mean all three of these compounds, which appear to act in concert. Commercial curcumin extracted from turmeric contains about 77%, 17%, and 6% of the three compounds, respectively.2

*A few of these studies have been discussed previously in Life Enhancement. See “Turmeric May Help Prevent Alzheimer’s and Parkinson’s Diseases” (February 2002), “Ancient Herbs Might Save Your Life” (April 2002), “Turmeric Protects Your Brain Cells” (July 2004), “Turmeric Is ‘The Spice of Life’” (November 2004), “Molecular Tools for Maintaining the Brain” (June 2005), “Why Your Stomach Will Love Turmeric and Licorice” (May 2006), “Galantamine Works Well in Real Life” (sidebar “Turmeric Fights Dementia,” February 2007), “Antioxidants Combat Age-Related Macular Degeneration” (April 2007), and “Turmeric’s Curcuminoids Help Prevent Brain Plaque” (October 2007).

Curcuminoids Hate Water . . .

The problem with curcuminoids is that they’re insoluble in water. When taken as a nutritional supplement, therefore, they tend to exist in the digestive tract—an aqueous environment—not as individual molecules but as undissolved particles from the powder. Most such particles are much too large to be absorbed through the intestinal wall into the bloodstream, so they wind up being excreted—a terrible waste. (For a primer on what happens when a molecule tries to gain access to the inner sanctum of your body, see the sidebar “Add Me This.”)

Add Me This

Four major factors contribute to the bioavailability of chemical compounds, whether they be nutrients (from food or supplements) or drugs. These factors are absorption, distribution, metabolism, and excretion, collectively called ADME (pronounced “add me”) in medical jargon.

To be absorbed into the bloodstream, a molecule must first survive a kind of chemical inferno: the hydrochloric acid and digestive enzymes of the upper gastrointestinal tract. Most proteins, complex carbohydrates, and fats—the principal constituents of food—do not survive as such—they’re decomposed to their constituent amino acids, simple carbohydrates, and fatty acids, respectively; these small molecules do survive.

The nutrient molecule, whatever its source, must then traverse the inner intestinal wall to gain access to the bloodstream. Specifically, it must pass through the walls of the surface epithelial cells, behind which are capillaries through whose walls it must also pass. These capillaries feed into the portal vein, which goes directly to the liver.

All cell walls are made of lipids, and the molecules most easily absorbed through them are of like kind: lipidic, or fat-soluble. The curcuminoids are in this category. But precisely because the curcuminoids are fat-soluble and not water-soluble, they tend to arrive at the cell walls in the form of relatively large, undissolved particles rather than as individual molecules. Such particles are very poorly absorbed.

One might think that water-soluble compounds (which are called hydrophilic, or “water-loving”) would be readily absorbed, because they arrive at the cell walls as individual molecules. But we’ve just seen that the cell walls are lipidic (hydrophobic, or “water-hating”), which means that they tend to repel not just water but also many compounds that are soluble in water. And many such compounds are, indeed, poorly absorbed.

Generally speaking, hydrophilic molecules dissolve easily in the GI tract but may be poorly absorbed, whereas hydrophobic molecules do not dissolve easily but would probably be readily absorbed if they did. What actually does wind up being absorbed, and at what rates, is the result of many delicate chemical balancing acts crafted by millions of years of evolution. Whether the nutrients are taken with or without food often makes a big difference, owing to the absorption-enhancing or absorption-inhibiting effects of other compounds in the intestinal “soup.”

Once in the bloodstream (after passing through the liver), most nutrients are not distributed uniformly throughout the body. This is especially true of lipidic compounds, such as the curcuminoids. Such compounds usually bind to various proteins in the blood, forming soluble lipid-protein complexes called lipoproteins.

Lipoproteins circulate freely, but because they interact with different organs and tissues in different ways and to different degrees, they tend to be unevenly distributed. Some tissues get more, some get less, depending on the exact nature of the lipoproteins’ chemical interactions with cell-surface receptors in the various tissues. Some tissues are especially difficult to reach, most notably those of the central nervous system, which is protected by the blood-brain barrier.

Now we must backtrack to the liver. Once a molecule has been absorbed from the intestines into the portal bloodstream, it goes to the liver, whose enzymes get first crack at all newcomers, changing many of them; this is called first-pass metabolism. For any given compound, the proportion of molecules changed can range from near-zero to near-total. Whatever the proportion, the molecular changes themselves can range from minimal to drastic in nature.

The result is that what emerges from the liver—some mix of the parent compound and its metabolites—may be very different from what went in. That could be good, bad, or indifferent, depending on whether the metabolites have better, worse, or the same effects (or no effect) as those of the parent compound. Once in the systemic circulation, further metabolism may occur, adding yet more layers of complexity to the problem.

Urine and feces are the main avenues of excretion, but sweat and breath serve this purpose for some compounds. In any case, excretion is not a simple matter, because there are many chemical feedback loops by which compounds on their way out get recycled for another pass through the system.

One way to compensate for this problem (which affects many other nutrients besides the curcuminoids) is to take massive amounts of the substance in question so that the tiny percentage that does get through will have an appreciable effect. But that’s impractical and expensive.

Some nutrients, including curcuminoids, can be formulated with another compound (called an adjuvant) that can enhance their bioavailability through favorable physical or chemical interactions. In one study, the bioavailability of curcumin in humans was boosted by 2000% by adding piperine (the compound that gives black pepper its pungency) to the formulation.3* In another study, piperine doubled the absorption of curcumin in humans—a much more modest gain of 100%, but still noteworthy.2

*In analogous experiments with rats, the improvement was only 154%, indicating that piperine was much more effective in improving the bioavailability of curcumin in humans than in rats. Can we draw any general conclusion from this fact regarding the relative responsiveness of humans vs. rats to pharmacological agents? Unfortunately no.

. . . But They Love Lipids

Another strategy for enhancing bioavailability is to disguise the substance in some other physical or chemical form that has a better chance of surviving nature’s gastrointestinal obstacle course. (It may not be nice to fool Mother Nature, but it can be worthwhile.)

A method that holds promise in this regard is to incorporate the curcuminoids into solid lipid nanospheres (SLNs). Curcuminoids dissolve readily in lipids (fats), to which cell walls are chemically hospitable. Nanospheres are tiny enough (in the size range of billionths of a meter) to have a modest shot at getting through the intestinal epithelial walls and into the bloodstream—if they haven’t already been degraded by pancreatic enzymes called lipases, which decompose fats to their constituent fatty acids.

If they do make it to the bloodstream largely intact, the SLNs will be further degraded, and most of their “payload” of dissolved curcuminoids will be released there instead of in the intestinal tract. (For more on this subject, see last month’s article “Solid-Lipid Nanospheres for Delivering Curcuminoids.”)

There are currently no published studies that support this scenario for curcuminoids, perhaps because most nanosphere research involves parenteral (other-than-oral) administration, which avoids the hazards of the GI tract altogether. There is, however, one encouraging study demonstrating a significantly enhanced bioavailability of vinpocetine (a synthetic alkaloid known primarily for its antidementia action) when it’s administered orally to rats in the form of SLNs.4

This Is Complex, Not Simple

Other studies offer tantalizing evidence for the potential value of SLN-formulated curcumin when taken orally. These studies entail the use of curcumin that is chemically complexed with a natural phospholipid, usually phosphatidylcholine (aka lecithin), which is the primary constituent of our cell walls. It’s important to note that a curcumin-phospholipid complex is a unique chemical entity—a different molecule—not to be confused with a physical mixture of curcumin and various lipids, as in SLNs. And these molecular complexes are dwarfed by SLNs, which typically contain tens of thousands to millions of molecules. The smaller the entity, the more likely it is to be absorbed, all else being equal. But curcumin-phospholipid complexes have a tendency to self-aggregate into large molecular clusters; where complexes are concerned, nothing is simple. (For more on the significance of complexes, see the sidebar “With This Chemical Bond I Thee Wed.”)

With This Chemical Bond I Thee Wed

What happens if you mix two chemical compounds that do not spontaneously react with each other? If they’re mutually soluble, like water and alcohol, they’ll form a solution. If not, the result might be an emulsion or some similar type of colloidal dispersion—a sol, perhaps, which is a solid dispersed in a liquid. With sols, a third compound that’s soluble in the solid but not in the liquid can sometimes be included in the mixing process so that it becomes incorporated, as a dissolved “payload,” into the dispersion.

For example, consider solid lipid nanospheres (a sol) as the dispersion, and curcumin as the payload, taken orally as a nutritional supplement. Because the curcumin is not chemically altered but is merely dissolved in the solid lipid, its chemical and physical properties remain unchanged, and it can manifest those properties when it’s liberated from the lipid. (Very little is known about where and when, and how rapidly, such liberation occurs in the body, except that it’s determined by many different factors.)

But there’s another way to combine the two compounds: by inducing a chemical reaction between them. Depending on the nature of the compounds and on the type of reaction, the result may be a special kind of entity that chemists call a complex. This is a molecule formed by the joining of two smaller molecules via a chemical bond that can, under the right conditions (such as a change in pH), be broken again so as to restore the two smaller molecules to their original state. In other words, the two smaller molecules are linked to each other but retain the ability to resume their original identities when they’re separated.

Nonetheless, because the complex is the product of a chemical reaction, it’s a new molecule that is distinctly different from either of the two smaller molecules. Its chemical and physical properties are unique, and it will behave differently (ideally, more favorably for the purpose at hand, such as being absorbed into the bloodstream) than its constituent molecules. Furthermore, a complex represents an exact ratio (usually 1:1) of the two constituent molecules, whereas a simple physical mixture of the two can exist in any ratio. That too is an important distinction.

A good analogy for a complex is a man and a woman who marry. When the bond of matrimony is formed between them, the man and woman are no longer quite the same—each is now part of the couple, which has different properties (physically, emotionally, socially, economically, legally, etc.) than either of them had alone. But the bond is not irrevocable—it can be broken by separation or divorce, restoring the man and woman to their earlier state (more or less).

The chemical process by which a complex is formed, by the way, is called conjugation. Sound familiar, as in “conjugal”? It comes from the Latin coniungere, meaning to join in marriage.

Improved Bioavailability and Liver Protection in Rats

In one study, researchers in China tested the bioavailability of curcumin alone, administered orally to rats, vs. that of a curcumin-phospholipid complex that contained the same weight of curcumin.5 They found that the peak plasma concentration of the complex was 125% higher than that of curcumin, and the complex remained in the circulation substantially longer than did the curcumin. Together, these factors indicated that the overall bioavailability of curcumin from the complex was 236% greater than from curcumin alone.

In another study, researchers in India prepared a curcumin-phosphatidylcholine complex and found that it was much more soluble in water than curcumin or a physical mixture of curcumin and phosphatidylcholine.6 When they administered these agents orally to rats, they found that the peak plasma concentration of the complex was 140% greater than that of curcumin, and it remained in the circulation much longer. The authors calculated that the overall bioavailability of curcumin was increased by 126% with the complex.

They found, furthermore, that the complex showed significantly stronger antioxidant activity than curcumin and that it provided significantly greater protection to the rats’ livers from damage caused by the administration of carbon tetrachloride, a toxic compound. They stated,

This enhanced therapeutic efficacy of curcumin in terms of hepatoprotection [liver protection] obtained from curcumin-phospholipid complex may be due to better absorption and bioavailability of the molecule, which was supported by the pharmacokinetic study in rats.

5-Fold Increase in Peak Plasma Curcumin Concentration

Finally, researchers in England undertook a detailed comparison of the bioavailabilities of curcumin and a commercially prepared curcumin-phosphatidylcholine complex in rats, using oral gavage (feeding via stomach tube) as the method of administration.7 They were motivated by their interest in curcumin’s remarkable record, in rodent studies, of helping to prevent cancer of the colon, skin, stomach, duodenum, soft palate, tongue, sebaceous glands, and breast. They also cited clinical (human) pilot studies showing an association between curcumin consumption and regression of premalignant lesions of the bladder, soft palate, stomach, cervix, and skin.

All those effects have been observed despite curcumin’s extremely low bioavailability, which the researchers naturally wished to enhance. They found that the novel curcumin-phosphatidylcholine complex they had chosen to use was very effective in this regard. The peak plasma concentration of curcumin was about 400% (5-fold) higher after administration of the complex than after administration of curcumin. The researchers pointed out, however, that this enhanced concentration was still well below those that have been shown to elicit pharmacological effects in cell-culture studies.

A major problem with curcumin’s bioavailability, in addition to its very poor absorption, is that what little curcumin does pass through the intestinal wall is extensively metabolized in the liver before it has a chance to reach the systemic circulation. Considering that the complex in the British study was much better absorbed than the curcumin, it came as no surprise that the complex produced plasma levels of four major curcumin metabolites that were 3 to 20 times higher than those resulting from curcumin alone. Whether or not these metabolites have biological activity akin to that of curcumin is unknown, but in the authors’ opinion, it’s likely that they do contribute to curcumin’s efficacy.

The authors stated, “It is conceivable that the improved bioavailability of curcumin, when administered as a complex with phospholipid, increases the potential scope of medical applications for curcumin.”

Never Stop Trying!

The studies discussed above are valuable because they lend credence to the idea that curcuminoids incorporated into solid lipid nanospheres consisting of phosphatidylcholine and other natural lipids may have greater bioavailability than unformulated curcuminoids. And anything that can improve the bioavailability of curcuminoids—or of any other poorly absorbed nutrients—is worth trying. Our parents’ efforts to get more and better nutrients into our systems began the day we were born, and we should keep up their good work.


  1. Aggarwal BB, Surh YJ, Shishodia S, eds. The Molecular Targets and Therapeutic Uses of Curcumin in Health and Disease. Vol. 595 of Advances in Experimental Medicine and Biology, Springer US, New York, 2007.
  2. Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB. Bioavailability of curcumin: problems and promises. Molec Pharmaceut 2007;4(6):807-18.
  3. Shoba G, Joy D, Joseph T, Majeed M, Rajendran R, Srinivas PS. Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Med 1998;64:353-6.
  4. Luo YF, Chen DW, Ren LX, Zhao XL, Qin J. Solid lipid nanoparticles for enhancing vinpocetine’s oral bioavailability. J Control Release 2006;114:53-9.
  5. Liu A, Lou H, Zhao L, Fan P. Validated LC/MS/MS assay for curcumin and tetrahydrocurcumin in rat plasma and application to pharmacokinetic study of phospholipid complex of curcumin. J Pharmaceut Biomed Anal 2006;40:720-7.
  6. Maiti K, Mukherjee K, Gantait A, Saha BP, Mukherjee PK. Curcumin-phospholipid complex: preparation, therapeutic evaluation, and pharmacokinetic study in rats. Int J Pharmaceut 2007;330:155-63.
  7. Marczylo TH, Verschoyle RD, Cooke DN, Morazzoni P, Steward WP, Gescher AJ. Comparison of systemic availability of curcumin with that of curcumin formulated with phosphatidylcholine. Cancer Chemother Pharmacol 2007;60:171-7.

Will Block is the publisher and editorial director of Life Enhancement magazine.

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