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Metabolites of EPA, DHA ripe area for innovation, expert says

By Hank Schultz , 17-Mar-2014
Last updated the 17-Mar-2014 at 04:03 GMT

Innovation in omega-3s has come in many forms.  New delivery modes, new raw material sources, and new chemical forms.  But through it all, the story has always been about  EPA and DHA as whole molecules. That might be about to change.

The next step in the diversification of the sector might be looking at ways to snip these molecules into more active metbolites, or at least facilitate that deconstruction within the body.  At the Next Innoation Summit in Anaheim, CA recently, Hector Lopez, principal and cofounder of Supplement Safety Solutions and the Center for Applied Health Sciences (along with Isaac Berzin of algae supplier Qualitas Health) spoke on new developements along this line.  

Early stage developments

In a subsequent interview with NutraIngredients-USA, Lopez laid out the challenges and opportunities that lie along this path. The field is at a germinal stage, with any product developments still a long way in the future. But being first to market in new fields means taking risks on technologies which might—or might not—come to fruition.

Dr Hector Lopez MD

The core of the idea comes from a sort of back-engineering, that is, looking at what omega-3s actually do in the body, Lopez said. Take the complicated set of reactions that occur at a site of injury or infection in the body. One cascade puts the immune system into defense and damage repair mode, another starts in as the process proceeds to cancel further contracts for those repair materials once the work is nearling completion and they are no longer needed. Failure to get those contracts cancelled in full is one of the mechanisms that can lead to to damaging, chronic low level systemic inflammation.

The body uses omega-3s as sources for smaller molecules that play key roles in this process, Lopez told NutraIngredients-USA. Using EPA and DHA as source materials, the body manufactures enzymatic epoxide/oxidation products such as so-called E-series and D-series resolvins, protectins, and maresins. 

“This is a class of small lipid molecules that are known as specialized pro-resolving mediators (SPMs),” Lopez said. “SPMs function as ‘firefighters’ to not only douse the ‘fire of inflammation’ but also clear ‘flammable debris’ from areas of tissue disruption/injury, infection, metabolic dysfunction or other insult.”

Instability a challenge

These molecules can be orders of magnitude more potent than their parent molecules, but they have very short half lives.  Once the immune system has been encouraged to return to homeostasis, they’re out of there. So the challenge to working them becomes, how do you package and deliver them?  And what might their regulatory status be?  Yes, they arise from substances—fish oils or other omega-3 sources—that have been used as an article of food.  But, given their flash-in-the-pan stability, they’ve never been around by themselves before.

All of that slants the exogenous delivery of these molecules toward the pharmaceutial space, Lopez said. Pharmaceutical companies would be looking to synthesize these molecules directly, he said.  And presumably significant investment would be required to encapsulate them in such a way they they could be shelf stable, and patent protection might be required to fund that and the safety and efficiacy studies for indications such as cancer, heart disease, auto immunie disorders and other conditions.

Botanical toolbox

But another pathway is available, Lopez said.

“My idea is that someone who wants to really harness the power of these mediators is going to come from a way to alter the enzymes endogesously that are repsonsible for this activity.  There are some botanical compounds that appear to upregulate the cyclooygenase enzymes to make them more efficient," he said. Lopez was coy about the particular botanical compounds as these are the subject of incipient intellectual property on the part of his group.

“We are looking to harness the enormous potential of this relatively novel area in fatty acid nutritional biochemistry, by providing a nutritional "toolbox" that includes providing both substrate (long-chain omega-3 essential fatty acids) plus botanical extracts that may encourage more efficient metabolism to yield SPMs when and where the body may need them most,” he said. 

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