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More scientific attention has been devoted to turmeric (Curcuma longa) than practically any other plant on Earth. Thousands of studies describing turmeric’s phytochemical and pharmacologic properties can be found in the literature, and researchers are still actively investigating its attributes. A member of the ginger family, turmeric has been known to Ayurvedic physicians for thousands of years, and it was undoubtedly used as a spice, food preservative and coloring agent long before it was ever exploited as a medicine.

Among the many pharmacologically active compounds found in turmeric, the curcuminoids—curcumin, demethoxycurcumin and bis-demethoxycurcumin—stand out as the most important. Of these, curcumin is the most abundant and the best studied. Over 100 molecular targets of curcumin have already been identified, and more will almost certainly be discovered. Nuclear factor kappa-B, cyclooxygenases, matrix metalloproteinases and many other pro-inflammatory mediators are inhibited by curcumin. These mediators are involved in the genesis and progression of most chronic human diseases, including diabetes, arthritis, cardiovascular disease, autoimmune conditions and cancer. Conversely, curcumin stimulates or up-regulates other mediators that reduce inflammation, alleviate oxidative stress or exert anticancer effects, such as Nrf-2 and heme oxygenase-1.

It’s no wonder some experts call turmeric (more specifically, curcumin) the “herbal panacea.” Few plants can boast such wide-ranging and seemingly universally salutary properties. Indeed, if all of the scientific data pertaining to this compound is to be believed, curcumin could be used to lower cholesterol levels, knock out inflammation, confer protection against infectious diseases, slow or prevent the development of dementia, ameliorate the impact of strokes and heart attacks and even prevent or treat cancer.

Unfortunately, the wellspring of curcumin’s diverse and near-miraculous physiologic properties--namely, its chemical structure--just happens to be its principal weakness. Curcumin is a polyphenolic, bis-α,β-unsaturated ketone that exists in equilibrium with its enol form in aqueous solutions and living tissue (see diagram below). Like many other plant-based polyphenols—catechins, tannins and ellagic acid, for example—native curcumin is poorly absorbed from the mammalian intestine. While curcumin’s limited absorption never stopped the Ayurvedics from recommending turmeric, it does cause headaches for scientists who want to demonstrate a connection between serum or tissue levels of curcumin and its purported health benefits. And this issue has been a particularly stubborn obstacle for the ever-avaricious pharmaceutical companies who recognize curcumin’s potential but have not yet developed derivatives possessing both clinical efficacy and high bioavailability.
 
Curcumin: One Shifty Molecule

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Oddly enough, the supplement industry may be ahead of Big Pharma on this one. Since supplement manufacturers don’t make their money by manipulating natural molecules and patenting the altered offspring, they’ve only needed to develop methodologies that improve native curcumin’s delivery to the bloodstream. (It should be stated here that simply ingesting curcumin with a bit of dietary fat will improve its absorption to some degree.) Very early on, scientists discovered that when curcumin is combined with piperine—the chemical that gives black pepper its pungency—its bioavailability improves by as much as 154%. Hence, a piperine-curcumin combination is as near as your favorite retail supplement outlet. However, some consumers’ stomachs don’t tolerate piperine very well, and bumping absorption 1 ½ times isn’t really all that impressive, so supplement purveyors have devised other approaches. 
 
One innovative manufacturer complexes curcumin with plant-based phosphatidylcholine to create microscopic, spherical “micelles” that chaperone curcumin across the intestinal barrier and into the bloodstream and tissues. (Phosphatidylcholine is a molecule that is naturally found within the cell membranes of both plants and animals.) These micelles, which are called Phytosomes®, improve curcumin absorption by nearly 30 times. Liposomal formulations composed of lipid bilayers surrounding a central repository of curcumin exploit the same concept as Phytosomes®. Other preparations combine micronized curcumin with essential oils from turmeric; still others deliver curcumin to the tissues in nanoparticulate vehicles.

Not surprisingly, there’s a lot of squabbling about whose curcumin formulation offers the best bioavailability and therapeutic efficacy. (Supplement makers are no different than Big Pharma in this regard: they all want to get a leg up on the competition.) Until the current industry-wide allegations of “fuzzy math” and “poor science” subside and this question is answered definitively, it’s a safe bet that any curcumin preparation that improves absorption without upsetting a person’s stomach is at least better than a raw extract.

As for the amount of curcumin one must consume in order to reap its protective benefits or address any particular health problem, this, too, is a matter for debate. Human studies have employed doses ranging from 500 to 12,000 mg daily with no evidence of toxicity; gastrointestinal distress (stomach pain or diarrhea) is the most common side effect seen in subjects taking high doses. Rare reports of stomach inflammation and ulcers have been linked to higher doses, as well. More bioavailable preparations will alleviate such problems, as lower doses can be used to attain equal or superior benefits in comparison to raw extracts. It’s prudent to follow label directions when taking a curcumin supplement.

While phytotherapeutic agents frequently interact with each other and with prescription medications, curcumin is remarkably free of serious herb-herb or herb-drug interactions. However, as with any other pharmacologically active substance, curcumin should not be consumed with utter impunity. Since curcumin inhibits cyclooxygenases, it may interfere with platelet function; anyone taking anticoagulants along with curcumin could be at increased risk for bleeding. In addition, some studies suggest that curcumin may interfere with the actions of certain chemotherapeutic agents, while others demonstrate curcumin’s ability to enhance the effects of both radiotherapy and chemotherapy. Therefore, patients receiving chemotherapy should always check with their physicians before taking curcumin. 
 
Since curcumin improves biliary clearance, people with gallstones or gallbladder disease should check with their healthcare providers before taking any supplements containing turmeric or curcumin. Finally, curcumin’s safety during pregnancy has not been evaluated; until more is known about curcumin’s effects on fetal development or pregnancy outcomes, it should only be used during pregnancy when the anticipated benefits clearly outweigh any risks.

References
  1. Cuomo J, Appendino G, Dern AS, et al. Comparative absorption of a standardized curcuminoid mixture and its lecithin formulation. J  Nat Prod. 2011 Apr 25;74(4):664-9
  2. Zhou H, Beevers CS, Huang S. The targets of curcumin. Curr Drug Targets. 2011 Mar 1;12(3):332-47
  3. Goel A, Aggarwal BB. Curcumin, the golden spice from Indian saffron, is a chemosensitizer and radiosensitizer for tumors and chemoprotector and radioprotector for normal organs. Nutr Cancer. 2010;62 7):919-30