Dietary Supplements and Bioavailability: Suppliers Improve Ingredient Bioavailability

Curcumin
Bioavailability is especially important for curcumin, which is notoriously difficult for the body to absorb. Standard curcumin is unstable at intestinal pH levels, resulting in rapid degradation. In addition, studies have shown that regular curcumin has a poor pharmacokinetic profile for oral absorption, a high rate of metabolic conjugation and reduction, as well as a tendency to be rapidly eliminated from the body, says Indena S.p.A. (Milan, Italy).

This fall, the company’s Meriva-brand curcumin was named best new product at the European Outsourcing Awards. Meriva utilizes Phytosome technology, which Indena says enhances curcumin’s bioavailability more than 20 times compared to standard curcumin extracts. Phytosome improves bioavailability through the use of soy phospholipids. Active ingredients are housed deep inside the phospholipid membrane’s bilayer, explains Federico Franceschi, PhD, senior scientist for Indena R&D.

“The resulting complex helps increase hydrolytical stability in the intestine, thereby reducing degradation,” says Franceschi. “Additionally, phospholipid complexation helps shuttle curcumin through biomembranes, overall improving oral bioavailability.”

More than 100 studies have shown Phytosome’s benefits on bioavailability, he adds. To test the bioavailability of Meriva with Phytosome, Indena compared its hydrolytical stability to standardized curcumin and found that Meriva increased hydrolytical stability in the intestine, increasing absorption. He says that the improved oral bioavailability has also been confirmed in pharmacokinetic studies and further validated in two consecutive clinical studies in which Meriva was shown to be active in the treatment of inflammatory conditions such as osteoarthritis and uveitis, at doses significantly lower than those associated with ordinary curcumin.

In October, Verdure Sciences (Noblesville, IN) launched Longvida, which the company calls an “optimized, next generation” curcumin that is absorbed by the body up to 65 times better than standard curcumin.

Lying behind the advanced bioavailability is Solid-Lipid Curcumin Particle (SLCP) technology, which the company developed together with neuroscientists from the University of California, Los Angeles. Thanks to SLCP, Longvida “solubilizes and stabilizes curcumin at the point in the gut where absorption is optimized,” says Blake Ebersole, technical director for Verdure.

During development, the company went through more than 200 test formulas, analyzing them in live models, including humans, against standard curcumin and placebo controls, he says.

Longvida was also tested in a study published online last January in the Journal of Agriculture and Food Chemistry. The trial included 11 subjects with osteosarcoma (bone cancer), as well as six healthy subjects. Researchers found that SLCP increased curcumin bioavailability in both test groups, stating, “Sustained levels of curcumin observed in our subjects and the nature of the SLCP suggest it continues to absorb into the bloodstream through the colon as it passes.”

According to Ebersole, testing curcumin bioavailability can be challenging. “It is very difficult to determine accurate amounts of free (unconjugated) curcumin in biological fluids compared to many other analytes,” he says. “Results must be interpreted correctly as well. For example, curcumin glucuronide is considered to be a relatively inactive metabolite of curcumin. So if the glucuronide is interpreted simply as curcumin, a given dose based on this misinterpreted blood-level data might not lead to the benefits that would be expected.”

Also in October, BioActives LLC (Worcester, MA) and Maypro Industries (Purchase, NY) launched Sustained-Release MicroActive curcumin, described as a “micronized, multistage time-released curcumin.”

The ingredient’s curcuminoids were solubilized to reduce their particle size. “A portion of the micronized particles are then encapsulated, creating an ingredient that releases in the stomach acid and then in the higher pH of the small intestine,” states the companies.

The enhanced bioavailability “is a combination of the nano size and the 12-hour sustained release that improves absorption,” says Jessie Rose, product specialist, proprietary ingredients, for Maypro. “The formulation of ingredients allows the curcumin to be slowly released in the stomach, and then released again and further absorbed in the small intestine.”

Rose says the companies conducted a dissolution test which compared the complex to a standardized curcumin extract of 95%, done using a “biorelevant medium” that she says closely correlates with in vivo uptake. The micronized curcumin showed release three times higher compared to control. Based on those results, the companies further planned to conduct a human clinical study in January to support bioavailability claims.

Vitamin K
Making headlines in October, Danisco’s (Copenhagen, Denmark) new ActivK ingredient is a long-chain menaquinone-7 (MK-7) form of vitamin K2 that is well absorbed.

Vitamin K sources can vary greatly in terms of bioavailability. K1 and K2 are the two main groups of naturally occurring vitamin K. When naturally derived from sources such as green leafy vegetables, vitamin K1 is poorly absorbed from these foods. (Synthetic vitamin K1, however, is easily absorbed.) “It is difficult for vitamin K1 from a natural plant source to be absorbed, primarily due to its tight binding to the chloroplasts in the leaves. Hence, only 10 to 20% of it can be absorbed, and the rest is excreted from the body,” explains Peter Wisler, director of business development for Danisco Health & Nutrition, Bioactives.

Comparatively, a vitamin K2 MK-7 ingredient like ActivK, derived from natto, is easily absorbed. “Vitamin K1, regardless of origin, has a very short half-life in the blood serum because its chemical structure (shorter side chains and bonds compared to vitamin K2 MK-7) is preferred by the liver. The liver makes a priority of using up K1, and hence, less of it is available to reach extrahepatic tissues, where it would initiate calcium absorption in bone mass,” Wisler explains.
“By contrast, vitamin K2, especially long-chained menaquinones such as MK-7, has a different molecular structure-longer lengths of the side chain and the bonds. As a result, MK-7 has a very long half-life in the blood and is not preferred by the liver. Therefore, it is distributed to the outer tissues and is available for activating the protein osteocalcin, which is needed to bind calcium to the bones.”

Lutein
Evidence is continually mounting of lutein’s benefits for increasing macular pigment optical density (MPOD), which is more often being considered a biomarker for eye conditions such as age-related macular degeneration (AMD). Lutein, however, must be bioavailable in order to reach the macula to provide its eye-health benefits, and like many ingredients, it is unstable in its purified form. As a result, manufacturers have used different methods of encapsulation to protect the lutein molecule, rendering it more bioavailable.

In October, Kemin Health LC (Des Moines, IA), the creator of FloraGLO-brand lutein, and DSM Nutritional Products (Parsippany, NJ) released a new study comparing FloraGLO’s bioavailability (utilizing DSM’s Actilease microencapsulation technology) to that of another lutein source.

Actilease formulates FloraGLO into microsized particles that are protected in a water-soluble, starch-matrix shell that acts like a sponge in which the lutein particles are embedded.

A randomized, double-blind, placebo-controlled, two-phase crossover trial was performed on 48 healthy subjects using either 20 mg of unesterified lutein in an alginate matrix, or FloraGLO lutein encapsulated using Actilease technology. The study found that lutein levels in the blood after FloraGLO treatment were 0.45 µmol/L (a 169.7% increase from baseline) versus a lower 0.23 µmol/L blood level (a 34.5% increase from baseline) after the alternative treatment.

“The comparative bioavailability of these two products, which only differ in their matrix composition, is significantly different,” says Diane Alexander, PhD, Kemin’s technical service manager. “These data really support the fact that all lutein sources are not equal, and they’re not equally bioavailable.”  

And, she says, bioavailability is sure to become a bigger issue for dietary supplements. “The NAD recently agreed with a challenge that a competitor lacked the bioavailablity data to support the health claims made for an ingredient in its supplement. We expect to see more of these actions in the future.”

The bottom line? “When shoppers purchase a supplement, they expect the supplement to deliver on its promised health benefits,” says Alexander. “In order to deliver on those benefits, the ingredient source should be bioavailable.”

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