Unknowns related to bioavailability enhancers troubles pharmacy researcher

11-Jul-2013 - Last updated on 20-Apr-2015 at 00:14 GMT

Piperine, an extract of black pepper, has been shown to boost bioavailability of other compounds.

Is bioavailability enhancement a cause for toxicological concern? It’s a question that came up for debate at the recent Toxicology Forum summer meeting in Aspen, CO. The answer was a highly qualified yes, when looking at a case-by-case basis.

It has been recognized for years that many dietary supplement ingredients that are highly touted for their health benefits, such as resveratrol and other polyphenols, curcuminoids and others, have in general poor bioavailability. Formulators have come up with a number of ingenious ways to get around this issue, some of which were detailed in a talk by Bill Gurley, PhD, a professor of pharmaceutical sciences at the University of Arkansas for Medical Sciences College of Pharmacy.

Among the bioenhancement methods Gurley looked at were:

Lipsomes
Phytosomes
Self emulsifying drug delivery systems
Nanoparticles
Phytochemical inhibitors of xenobiotic metabolism, such as piperine.

The issue for Gurley, who is also a member of the United States Pharmacopoeia’s Expert Panel on Dietary Supplements, is that the boost these technologies provide to the ingredients to which they are applied is not always known to someone in his position, making evaluating cases of possible liver toxicity and potential negative herb-drug interactions tricky.

“Piperine (for example) on its own is fairly innocuous. It’s not a question of the toxicity of piperine, it’s a question of how it enhances the bioavailability of other compounds. There may be some toxicological concern there; we just don’t know,” Gurley said.

“There are some studies that show the effect of piperine with certain drugs, and enhancing their bioavailability; but that’s just a classic case of herb-drug interaction.”

Suppliers: data is available

Sabinsa Corp. markets one of these bioenhancers: BioPerine, a black pepper extract. When used in conjunction with curcumin it has a powerful effect.

“(Bioperine’s) function is not limited to particular class of compounds, and its effect has been of great interest in the compounds which have a poor absorption profile, such as curcumin and resveratrol. As per the published report in Planta medica 1998, Curcumin’s bioavailability was found to be increased by 20 fold or 2000%. The increase in bioavailability may vary from compound to compound,” said Anurag Pande, PhD, vice president of scientific affairs for Sabinsa.

"Our customers who are looking to add BioPerine in their formulations are provided information on Bioperine’s role as bioavailability enhancer, its dosage and clinical studies to help them understand the product better," Pande said. A reseach team at Tufts found no negative herb/drug interactions between a curcumin/BioPerine combo and over the counter drugs such as Acetaminophen, Flurbiprofen, and Midazolam.

Dr. Paolo Morazzoni, scientific director of Indena, had this to say about the company’s phytosome bioenhancement technology:

"When dealing with widely used standardized extracts, we refer to toxicological data generated (by Indena itself or already reported in literature) on the standardized native extracts. These tests are usually conducted by using a very large window of dosages allowing to cover an eventual increase of bioavailability by 2-4 times obtainable with the phytosomal formulations.”

If the phytosome proves to boost bioavailability in excess of that range, new toxicological studies are conducted, Morazzoni said. Similarly, for phytosomes constructed with novel or innovative extracts, new tox data is needed, he said.

Simple calculation

If hard data on the bioavailability boost is available, making a toxicological judgment could be pretty straightforward, said Andrea Wong, PhD, senior scientific and regulatory consultant with Intertek Cantox.

“In some cases, if you have the data, it can be as simple as doing a calculation,” she said. “You can just multiply accordingly to determine if the available information is still sufficient to support a determination of the safety of the ingredient.

“But you have to take a look at whether you can quantify how much more bioavailable it is via a validated method,” she said.

Unknown territory

So while some data is available on what these bioenhancers do, there are still many unknowns, which is troubling to someone like Gurley, who deals with the rare cases of injuries associated with supplement use. As other participants at the forum noted, it’s cold comfort to someone who’s sick to be told that theirs is a unusual case.

“What’s concerns me is if you had (for example) a weight loss product that’s formulated with piperine but it’s also adulterated. In that case I think the toxicological situation is just completely unknown,” Gurley said.