Clinical Uses for a Novel Form of Bioavailable Curcumin

Gaetano Morello, ND

Turmeric has a long history of medicinal use in both Ayurvedic and Traditional Chinese Medicine. Dubbed the “herb of the sun” because of its deep yellow hue, turmeric is the dried and ground rhizome of the perennial herb Curcuma longa. Traditionally, this member of the ginger family (Zingiberaceae) has been used to treat a wide variety of maladies, including anorexia, arthritis, chronic sinusitis, indigestion, liver conditions, skin diseases, ulcers, urinary disorders, and wounds. Modern medicine has taken note of turmeric’s anti-inflammatory and antioxidant actions. In 1985, the German Commission E approved the herb for use in cases of indigestion.1 Turmeric has also been suggested as a safe and effective alternative to nonsteroidal anti-inflammatory drugs like celecoxib, ibuprofen, and aspirin.1

The primary constituent in turmeric responsible for these actions is curcumin (also known as diferuloylmethane), an umbrella term used to denote the totality of phenolic curcuminoids found in the rhizome. There are 3 primary curcuminoids, of which curcumin is the most extensively researched; the others include demethoxycurcumin and bis-demethoxycurcumin. Curcumin is not only responsible for turmeric’s rich yellow-orange color, it is also what gives the plant its powerful anti-inflammatory properties. Evidence shows that curcumin downregulates cyclooxygenase 2 and inducible nitric oxide synthase enzymes, likely by suppressing nuclear factor-kappaB activations.2 It also inhibits arachidonic acid metabolism, scavenges free radicals, promotes apoptosis, and inhibits the production of inflammatory cytokines, tumor necrosis factor, and interleukins.3,4

These actions give curcumin a great deal of clinical potential. Indeed, recent animal and human studies5-9 have shown promise for the treatment of Alzheimer disease, diabetes mellitus, osteoarthritis, and ulcerative colitis, as well as several types of cancer. Yet, curcumin’s usefulness in a real-world clinical setting has historically been limited because of its low systemic bioavailability, even at gram dosages.

The Bioavailability Conundrum

Human investigations have shown that curcumin is not only poorly absorbed but also has poor systemic bioavailability. This is in part due to the fact that curcumin is rapidly metabolized and quickly conjugated in the liver, resulting in metabolites (curcumin glucuronide and curcumin sulfates) that may not have the same biological activity as the parent compound. What is more, curcumin is quickly eliminated by the body. However, if curcumin reaches the bloodstream, it is not only stable but also has the ability to enter difficult-to-penetrate tissues like the brain. The challenge, therefore, has been to create a stable, readily absorbable form of curcumin that can be delivered to plasma without the use of synthetic agents or substances that are otherwise undesirable.

Several strategies have been used to improve curcumin’s bioavailability, with varying degrees of success. These include the use of adjuvants (like piperine) that interfere with glucuronidation, liposomal curcumin, and curcumin-phospholipid complexes.10 A novel approach has been the use of colloidal dispersion technology, creating a water-dispersible curcumin that dramatically enhances absorption and bioavailability. This innovative preparation is created by finely milling turmeric, then mixing it with glycerin and gum ghatti, a natural polysaccharide-rich vegetable gum obtained from the sap of the ghatti tree (Anogeissus latifolia) to form a colloid. The resulting water-dispersible curcumin is very stable against light and heat, is exceptionally dispersible and stable in water, and is at least 27 times more bioavailable in humans than standard curcumin, giving it the potential to exert benefits at considerably lower doses than other forms.11

In a double-blind trial,12 a total of 14 middle-aged subjects were randomized to receive 30 mg of curcumin from either a standard curcumin powder or in the form of a water-dispersible turmeric colloid (Theracurmin13). Blood samples were collected before dosing and at 1, 2, 4, 6, and 24 hours after administration. The 24-hour plasma area under the curve (AUC) of the water-dispersible curcumin (113 ng/mL) after a single dose was 27-fold higher than that of standard curcumin (4.1 ng/mL). The maximum concentration of drug was 29.5 ng/mL compared with 1.8 ng/mL for standard curcumin. Water-dispersible curcumin reached the time of occurrence for maximum (peak) drug concentration in 1 hour compared with 6 hours for standard curcumin.

It remained to be determined whether higher doses of water-dispersible turmeric could safely increase plasma curcumin levels in a dose-dependent manner. Kanai and colleagues14 gave 2 doses of water-dispersible curcumin (providing 150 mg of curcumin and [2 weeks later] 210 mg of curcumin, respectively) to human volunteers. The 24-hour AUC for the 150-mg dose was 2649 ng/mL, and the 24-hour AUC for the 210-mg dose was 3649 ng/mL. The researchers concluded that water-dispersible turmeric colloid safely increased plasma curcumin levels in a dose-dependent manner without saturating the absorption system. Higher doses were found to have higher bioavailability, and no upper limit on this increase has yet been established.

Clinical Applications

Several clinical trials of water-dispersible curcumin have been conducted, with some that are still ongoing. In a crossover study11 of 7 participants, 300 mg of water-dispersible turmeric (delivering 30 mg of curcumin) protected against adverse effects of alcohol intoxication when taken before alcohol consumption, as evidenced by reduced acetaldehyde concentration of the blood. Another study15 of 19 healthy volunteers found that key markers of liver function (such as gamma-glutamyl-transpeptidase, aspartate transaminase, and alanine transaminase) decreased after taking 900 mg of water-dispersible turmeric (providing 90 mg of curcumin) twice daily for 1 month, with little lifestyle modification. Furthermore, liver function markedly improved in subjects who had higher baseline values than in relatively healthy ones. This same study also found that taking either 300 mg or 900 mg of this innovative form of curcumin resulted in a 15% boost in skin moisture. In addition, the researchers noted a dose-dependent improvement in facial discoloration, wrinkles, and pores.

Other research has focused on the ability of water-dispersible curcumin to heighten the benefits of exercise. One pilot study16 investigated its effects on central arterial hemodynamics. The placebo-controlled trial, which involved 45 postmenopausal women, found that regular endurance exercise combined with daily curcumin ingestion lowered the age-related increase in left ventricular afterload to a greater extent than monotherapy with either curcumin or exercise alone.

A pilot study (Theravalues Corporation, unpublished data on file) of 14 young, unconditioned men examined the effects of water-dispersible turmeric on muscle recovery after intense exercise. The participants took a dose of either 150 mg of curcumin or placebo immediately before exercising and again 12 hours after maximal bicep-flexion exercise. The researchers found a significantly greater percentage of change in maximal voluntary muscle contraction in the curcumin group compared with the placebo group. Curcumin also improved biochemical indexes of muscle recovery compared with placebo. These included creatine kinase, lactate dehydrogenase, and creatine kinase MB fraction 72 hours after exercise.

Ongoing Research

Two additional clinical trials of this innovative water-dispersible turmeric are ongoing. The first, sponsored by the MD Anderson Cancer Center, Houston, Texas, is a phase 1 study13 evaluating its effect in patients with advanced cancers for whom 1 or more prior therapies have failed or for which there is no established standard-of-care therapy. The second is an 18-month study17 sponsored by the University of California, Los Angeles, evaluating the effects of water-dispersible turmeric on cognitive function in 132 subjects (age range, 50-90 years) with age-associated memory complaints. The outcomes of these studies, as well as additional human research, will provide practitioners with additional evidence on how this highly bioavailable form of curcumin may effectively benefit patients. Optimizing its biological activity through an effective delivery system means that curcumin may finally fulfill its potential to successfully treat a wide variety of conditions in clinical settings.


Morello_HeadshotGaetano Morello, ND is a naturopathic physician practicing in West Vancouver, British Columbia, Canada. He received his bachelor of science degree from the University of British Columbia (Vancouver) and his doctor of naturopathic medicine from Bastyr University of Natural Health Sciences in Seattle, Washington. Since 1991, Dr Morello has been training and educating physicians, pharmacists, and health experts on the scientific use of natural medicines in the fields of cardiology, immunology, gastroenterology, antiaging, and detoxification. A contributing author to the authoritative text on alternative medicine, A Textbook of Natural Medicine, he is also author of The Fiber Miracle.

References

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