Over the last decade, few dietary supplements have been in the news as much as curcumin and turmeric, the item from which curcumin and related compounds are extracted. The background for modern western interest is much older. Turmeric (Curcuma longa) is a yellow spice and a traditional remedy that has been used as a medicine, condiment and flavoring since 600 BC. The rhizome (underground stem) is the part of the plant that is harvested and ground to make the spice. In the Indian Ayurvedic tradition of healing and cooking, the yellow spice turmeric warms and activates the digestion and is useful in many aspects of healing. Both Ayurveda and Traditional Chinese Medicine (TCM) associate turmeric with the health of the liver, skin, digestive, lung, joint and muscle tissues.
Some of the key bioactive constituents found in turmeric are three kinds of curcuminoids, curcumin, demethoxylcurcumin, and bisdemethoxylcurcumin. All three components are structurally similar, although curcumin seems to be the most effective of these three. Curcumin and the related curcuminoids (the mention of curcumin often being shorthand for all three) appear to affect human health through antioxidant activity and possible modulation of 5-lipo-oxygenase (LOX) and cyclo-oxygenase (COX) enzymes. The true health potential of curcuminoids has always been hindered by notoriously poor oral bioavailability. This has become generally accepted in recent years with numerous studies in humans demonstrating severe absorption shortcomings even when curcumin is consumed in large quantities. As a result, researchers have sought ways to overcome this limitation in bioavailability.
Too often overlooked with the focus on turmeric's curcuminoids is the presence of a number of other bioactives in the rhizome. These include immune-stimulating polysaccharides, volatile oils and yet other constituents. Beyond conventional turmeric lie one or more related species, such as Indonesia's Java turmeric, which exhibit special benefits not associated with Indian turmeric.
Curcumin and the Curcuminoids
Curcuminoid bioavailability is low for a variety of reasons. First, solubility in water is quite poor, especially so at the low pH (acid conditions) found in the stomach. Once food leaves the stomach, the pH rises in the upper small intestine and this presents other challenges inasmuch as curcuminoids are subject to damage by digestive fluids under these more neutral conditions. To make matters worse, poor absorption is compounded by their quick excretion from the system. The preponderance of the curcuminoids that are consumed is eliminated intact from the gut. Some curcuminoids are absorbed into the circulation, but almost none can be found in the blood in their free forms. Instead, they are almost entirely converted into water-soluble metabolites in the intestine and liver and appear in the blood as glucuronide forms.
Curcuminoids exhibit strong antioxidant activity, enhance cellular resistance to oxidative damage, and provide antioxidant protection against DNA damage. They also enhance the body's natural antioxidant glutathione levels, which in turn aids the liver in detoxification. Joint health is one area of significant benefit. In research on people with suboptimal joint function, curcuminoids have been found to support a healthy inflammatory response while promoting comfort and flexibility. There are many other areas of benefits. Curcuminoids exert several protective effects on the gastrointestinal tract, most likely via antioxidant activity. A double-blind trial found turmeric helpful for people with indigestion and effective in animal research in promoting healthy digestive function. Via antioxidant activity, curcuminoids may help promote cardiovascular health, especially by decreasing the propensity of low density lipoprotein (LDL) to oxidize. Research continues to suggest that oxidized LDL is one of the more pernicious forms of cholesterol in relation to cardiovascular health. The benefits of most interest, albeit ones that cannot be mentioned directly for any dietary supplement due to FDA regulations, are in the area of cancer.
Success in translating these potentials into tangible results has been limited by inherently poor intestinal absorption, rapid metabolism, and limited systemic bioavailability. These factors help to account for the somewhat spotty record of curcumin in clinical trials. Seeking to overcome these limitations, food ingredient formulators have begun to employ a variety of approaches for enhancing absorption and bioactivity. Many of these strategies are attempts to improve upon the age-old practice of consuming turmeric in fat-based sauces, such as in fat-rich curries. However, there exists uncertainty as to how the various commercially available offerings compare to each other in terms of either uptake or efficacy and this uncertainty leaves lay individuals, physicians and nutritionists with a dearth of data for evaluating products. A typical conundrum: is bioavailability calculated based on the active ingredient(s) only or on the total volume of a formula? Five times the bioavailability may not be an advance if it requires a formula with five times the weight for delivery, e.g., taking one capsule of curcuminoids versus taking five capsules to deliver the same amount of curcuminoids in four capsules worth of excipients.Controversies
Readers need to be extremely cautious regarding marketing claims as to the efficacy and bioavailability of curcumin products. For instance, one manufacturer of a curcumin product claims to offer a delivery format that upon ingestion leads to relatively large amounts of free curcumin in the blood, yet almost all other research indicates that the three curcuminoids are subject to rapid metabolism, both intestinal and hepatic. This means that almost no free curcumin can be found in the blood, only various metabolites and conjugates of these curcuminoids.1,2 Are these metabolites active? Curcumin metabolites retain at least some biological activity, but whether curcumin metabolites are as active as curcumin itself is not yet clear.3,4,5,6,7,8,9 In fact, the phenomenon in which turmeric extracts produce undetectable levels of free curcumin in plasma and nevertheless exhibit clinically significant effects speaks in favor of the biological relevance of curcuminoid metabolites.10,11,12 Still, it is doubtful that the conjugates of curcuminoids are able to pass the blood-brain barrier.13 This latter factor suggests that at least some of the benefits attributed to regular turmeric consumption via the diet are not derived from the curcuminoids.
More traps for the unwary abound. For example, rodentbased studies of bioavailability can be misleading due to the fact that rodents exhibit different curcumin pharmacokinetics compared to humans.14 Sometimes even claims regarding increased bioavailability in humans have failed spectacularly when revisited. One such claim is that inclusion of black pepper or one of its constituents, i.e., piperine (Bioperine), improves curcumin uptake. An early research study reported that a small quantity of piperine can enhance curcumin bioavailability "20-fold" in humans.15 In opposition to this conclusion, a recent independent analysis reported finding little increase in plasma free curcuminoid levels when using the commercially available C 3 Complex plus piperine systems.16 As another example of the issues that can arise is an ambiguous representation of the dosage tested in clinical trials. On this point, see the letters in a recent controversy over claims for a particular curcumin for exercise-induced muscle damage based on published research in which the dosages administered were, at the very least, unclear.17
Dietary Supplement Options
Various supplement options are examined in detail in "Beyond Yellow Curry: Assessing Commercial Curcumin Absorption Technologies," which can be freely downloaded from PubMed.18 This article and related background research suggest that particularly noteworthy commercial products based on concentrated curcuminoids include CurcuWIN™ (OmniActive Health Technology),19 Meriva® (Indena) and Theracurmin™ (Theravalues/P.L. Thomas).
What About Whole Turmeric?
Great emphasis has been placed on the curcuminoids found in turmeric, so much so that the average person might well believe that there is little else of worth in this spice. Nothing could be further from the truth! There are at least 200 known compounds in turmeric root, dozens of which appear to be active. Aside from the three major curcuminoids, known active compounds and families of compounds in turmeric include â-elemene, bisacurone, calebin A, curcumene, curdione, cyclocurcumin, volatile/fixed oils (turmerones and related compounds), bisabocurcumin, various proteins (biologically active molecular carriers, etc.), special dietary fibers (enhancers of the bioavailability of biologically active molecules), and acidic polysaccharides (immunomodulators).20
According to one company involved in advanced product development in conjunction with the famous curcumin researcher, Bharat B. Aggarwal, "the challenge is to recreate the curcumin inside the turmeric matrix effectively." It claims to have developed a novel way to recreate the turmeric matrix with active curcuminoids by a method known as Polar- Nonpolar Sandwich (PNS) technology. Potential benefits of this product, known by two different names, Cureit and Acumin (the latter in the American market via Novel Ingredients), are likely to be much broader than those that can be traced to curcuminoids alone. This approach has been discussed in these pages before—see "Beyond Synergy–the Entourage Effect in Nutrition and Herbalism" (TotalHealth Sep 2015). This new item, which consists of nothing other than specially treated turmeric without the addition of piperine, nanoparticles, liposomes, micelles, phospholipid complexes or their analogs, is being presented as supporting bone and joint health, cognitive function and general anti-aging benefits.21
Several clinical studies have been completed, although not yet published. A study conducted in rheumatoid arthritis patients showed that Acumin was beneficial. Active rheumatoid arthritis patients who received Acumin (either 250 or 500 mg twice per day) for a period of 90 days reported a statistically significant decrease in their clinical symptoms towards the end of the study.22 This result is similar to that reported with the use of 1,000 mg of a special delivery curcumin preparations, such as Meriva, over the same time range.23 Another Acumin clinical study examined comparative bioavailability issues, although these may not be particularly relevant given that Acumin is not a pure curcuminoid product. Both of these studies currently are under review for publication.Because the Western pharmaceutical approach focuses on purified components rather than on matrixes of components, at the moment there is much more available research on curcuminoids than on turmeric as such. However, there is a growing body of evidence indicating the benefits of active compounds other than curcuminoids found in turmeric. Those who want the "entourage effect" and would like to try the whole herb approach with an activated turmeric now have an alternative to the regular consumption of curries and golden milk.
Beyond Indian turmeric, there is a related item that in at least one traditional Asian medical system is considered to be superior for many health purposes. Known as Java turmeric or Javanese turmeric due to its origins in Indonesia, C. xanthorrhiza is a plant of the ginger family Zingiberaceae, which grows widely in Southeast Asia. Java turmeric is related to the better known Indian turmeric and there is a large overlap in traditional and modern herbal uses, including anti-inflammatory, anticarcinogenic, wound healing and serum cholesterol-lowering.24 A number of constituents differ between Java and ordinary turmeric. Xanthorrhizol, in particular, is a sesquiterpenoid compound unique to Java turmeric. Among its known special benefits are hepatoprotective actions. An extract of the whole rhizome, likewise, has been shown to support liver health.25
An area that has been under-explored with Java turmeric, but in which this plant may exhibit special benefits, is immune function. For instance, in one animal experiment, chronic ingestion of an extract increased the proportion of splenic T cells.26 An in vitro trial examining mechanisms of action for immune response found that a polysaccharide in Java turmeric stimulates the immune functions of macrophages.27 Among the differences between Java turmeric and Indian turmeric are the following:
- composition of the dried rhizome—curcuminoids (1.6–2.2 percent), xanthorrhizol (1.48–1.63 percent)
- three nonphenolic diarylhepatanoids support normal inflammation response
- acceleration of the metabolism of the lipids from extrahepatic tissues to the liver, thus increasing the excretion of cholesterol via the bile
- secretion of bile acids (and bilirubin) and improvement in bile composition leading to the cholesterol found in bile being more likely to remain in solution (important for gallbladder function)
- unlike bisdesmethoxycurcumin, does not inhibit bile flow
In powdered bulk form and other deliveries, Java turmeric has been available in the US via specialized Asian product sellers for decades and in Europe for centuries. (Indonesia was under Dutch rule from the mid-17th Century until 1949.) CUR-XZOL™ (Curcuma xanthorrhiza Roxb.) is a commercially available source of Java that is manufactured in a major Indonesian pharmaceutical facility. It is fully characterized and contains a specified amount of xanthorrhizol. On amazon.com it can be found in an American formula as "WILD JAVA TURMERIC."References
- Ireson CR, Jones DJ, Orr S, et al. Metabolism of the cancer chemopreventive agent curcumin in human and rat intestine. Cancer Epidemiol Biomarkers Prev 2002;11(1):105–11.
- Pan MH, Huang TM, Lin JK. Biotransformation of curcumin through reduction and glucuronidation in mice. Drug Metab Dispos 1999;27(4):486–94.
- Ireson C, Orr S, Jones DJ, et al. Characterization of metabolites of the chemopreventive agent curcumin in human and rat hepatocytes and in the rat in vivo, and evaluation of their ability to inhibit phorbol ester-induced prostaglandin E2 production. Cancer Res 2001;61(3):1058–64.
- Sandur SK, Pandey MK, Sung B et al. Curcumin, Demethoxycurcumin, Bisdemothoxycurcumin, Tetrahydrocurcumin, and Turmerones Differentially Regulate Anti-inflammatory and Antiproliferative Responses Through a ROS-Independent Mechanism. Carcinogenesis 2007 Aug;28(8):1765–73.
- Sugiyama Y, Kawakishi S, Osawa T. Involvement of the beta-diketone moiety in the antioxidative mechanism of tetrahydrocurcumin. Biochem Pharmacol. 1996 Aug 23;52(4):519–25.
- Pfeiffer E, Hoehle SI, Walch SG, Riess A, Sólyom AM, Metzler M. Curcuminoids form reactive glucuronides in vitro. J Agric Food Chem. 2007 Jan 24;55(2):538–44.
- Kim JM, Araki S, Kim DJ, Park CB, Takasuka N, Baba-Toriyama H, Ota T, Nir Z, Khachik F, Shimidzu N, Tanaka Y, Osawa T, Uraji T, Murakoshi M, Nishino H, Tsuda H. Chemopreventive effects of carotenoids and curcumins on mouse colon carcinogenesis after 1,2-dimethylhydrazine initiation. Carcinogenesis. 1998 Jan;19(1):81–5.
- Pari L, Amali DR. Protective role of tetrahydrocurcumin (THC) an active principle of turmeric on chloroquine induced hepatotoxicity in rats. J Pharm Pharm Sci. 2005 Apr 30;8(1):115–23.
- Murugan P, Pari L. Effect of tetrahydrocurcumin on plasma antioxidants in streptozotocin-nicotinamide experimental diabetes. J Basic Clin Physiol Pharmacol. 2006;17(4):231–44.
- Sharma RA, McLelland HR, Hill KA, Ireson CR, Euden SA, Manson MM, Pirmohamed M, Marnett LJ, Gescher AJ, Steward WP. Pharmacodynamic and pharmacokinetic study of oral Curcuma extract in patients with colorectal cancer. Clin Cancer Res. 2001 Jul;7(7):1894–900.
- Mohammadi A, Sahebkar A, Iranshahi M, et al. Effects of Supplementation with Curcuminoids on Dyslipidemia in Obese Patients: A Randomized Crossover Trial. Phytother Res. 2013 Mar;27(3):374–9.
- Sharma RA, Euden SA, Platton SL, et al. Phase I clinical trial of oral curcumin: biomarkers of systemic activity and compliance. Clin Cancer Res 2004;10:6847–54.
- Pan MH, Huang TM, Lin JK. Biotransformation of curcumin through reduction and glucuronidation in mice. Drug Metab Dispos. 1999 Apr;27(4):486–94.
- Ireson CR, Jones DJ, Orr S, et al. Metabolism of the cancer chemopreventive agent curcumin in human and rat intestine. Cancer Epidemiol Biomarkers Prev 2002;11(1):105–11.
- Shoba G, Joy D, Joseph T, et al. Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Med 1998;64:353–6.
- Volak LP, Hanley MJ, Masse G, Hazarika S, Harmatz JS, Badmaev V, Majeed M, Greenblatt DJ, Court MH. Effect of a herbal extract containing curcumin and piperine on midazolam, flurbiprofen and paracetamol (acetaminophen) pharmacokinetics in healthy volunteers. Br J Clin Pharmacol. 2013 Feb;75(2):450–62.
- Douglass BJ, Clouatre DL. Beyond Yellow Curry: Assessing Commercial Curcumin Absorption Technologies. J Am Coll Nutr. 2015;34(4):347–58. Downloadable from https://www.ncbi.nlm.nih.gov/pubmed/25856323.
- Oliver JM, Stoner L, Rowlands DS, Caldwell AR, Sanders E, Kreutzer A, Mitchell JB, Purpura M, Jäger R. Novel Form of Curcumin Improves Endothelial Function in Young, Healthy Individuals: A Double-Blind Placebo Controlled Study. J Nutr Metab. 2016;2016:1089653.
- http://www.aureabiolabs.com/wp-content/uploads/2016/10/Aurea-Newsletter_August.pdf and http://www.aureabiolabs.com/wpcontent/uploads/2016/08/Aurea-Newsletter_June.pdf
- Belcaro G, Cesarone MR, Dugall M, Pellegrini L, Ledda A, Grossi MG, Togni S, Appendino G. Product-evaluation registry of Meriva®, a curcumin-phosphatidylcholine complex, for the complementary management of osteoarthritis. Panminerva Med. 2010 Jun;52(2 Suppl 1):55–62.
- Oon SF, Nallappan M, Tee TT, Shohaimi S, Kassim NK, Sa'ariwijaya MS, Cheah YH. Xanthorrhizol: a review of its pharmacological activities and anticancer properties. Cancer Cell Int. 2015 Oct 21;15:100.
- Devaraj S, Ismail S, Ramanathan S, Marimuthu S, Fei YM. Evaluation of the hepatoprotective activity of standardized ethanolic extract of Curcuma xanthorrhiza Roxb. Journal of Medicinal Plants Research 2010 December;4(23):2512–7.
- Yasni S, Yoshiie K, Oda H, Sugano M, Imaizumi K. Dietary Curcuma xanthorrhiza Roxb. increases mitogenic responses of splenic lymphocytes in rats, and alters populations of the lymphocytes in mice. J Nutr Sci Vitaminol (Tokyo). 1993 Aug;39(4):345–54.
- Kim AJ, Kim YO, Shim JS, Hwang JK. Immunostimulating activity of crude polysaccharide extract isolated from Curcuma xanthorrhiza Roxb. Biosci Biotechnol Biochem. 2007 Jun;71(6):1428–38.
Curcumin, Turmeric and Beyond
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Dallas Clouatre, PhD
Dallas Clouatre, Ph.D. earned his A.B. from Stanford and his Ph.D. from the University of California at Berkeley. A Fellow of the American College of Nutrition, he is a prominent industry consultant in the US, Europe, and Asia, and is a sought-after speaker and spokesperson. He is the author of numerous books. Recent publications include "Tocotrienols in Vitamin E: Hype or Science?" and "Vitamin E – Natural vs. Synthetic" in Tocotrienols: Vitamin E Beyond Tocopherols (2008), "Grape Seed Extract" in the Encyclopedia Of Dietary Supplements (2005), "Kava Kava: Examining New Reports of Toxicity" in Toxicology Letters (2004) and Anti-Fat Nutrients (4th edition).