Marketers of probiotic dietary supplements have often remarked that a large percentage of the body’s immune system resides in the gut. To the uninitiated this is a revelation, but when you look at it from a common sense standpoint, how could it be otherwise? The mouth is the main avenue (along with the lungs) by which infectious organisms enter the body. If you were a general, wouldn’t you station your troops in the sector where you are most likely to be attacked?
And prime among those defenses is the stomach itself. The gastric juices, made up of hydrochloric acid, enzymes and other constiuents, creates an environment in which many microorganisms die off. In addition to jumpstarting digestion by denaturing proteins, the gastric fluid helped our forebears to eat foods not even remotely up to modern sanitary standards and still escape (for the most part) debilitating or fatal infections.
So circumventing this defense mechanism with the power of evolution behind it has become a goal for probiotic delivery system innovators. But first, they had to conquer the stability question, no mean feat for dormant organisms that are seeking any wisp of moisture to germinate.
Room for all
“There will always be an audience for all of the probiotic dosage forms as long as manufacturers are following GMPs, as long as the producers can show stability throughout the shelf life,” George Paraskevakos, executive director of the International Probiotics Association told NutraIngredients-USA. Assuming that those quality standards are met, consumers can find a measure of success even with low-tech delivery modes, such as standard capsules.
“There is a small window after you eat where the acidity in your stomach goes down. Even with your regular run-of-the-mill capsule, a conventional dosage delivery form that we all know will come apart pretty quickly in the stomach, if you take it shortly after you eat, when the pH of the stomach has gone from a 2 to something like a 5 or 6, a lot of those organisms will get through,” he said.
There has been a wealth of innovation regarding probiotics in food. One recent step forward that is almost ready for market is a probiotic straw system offered by Australian firm Unistraw. It’s a way to get probiotics in RTD shelf stable beverages. Boulder-based Next Foods has been doing this for years with its Good Belly line of juice drinks, but they require refrigeration. Unistraw has a system to allow probiotics to be delivered with a RTD milk or other beverage in a TetraPak container with a loaded straw ready to jab in.
“It’s a beading process,” said Carl Freund, president of Unistraw North America. “We have two years of data on the straws. Probiotics don’t take up much room, so we can easily deliver 2 billion CFUs as well as the flavor for the product on the inside of the straw.”
BioGaia also offers probiotic straws packaged in their own container.
Just how many organisms get through the stomach gantlet via these approaches is the question. It hasn’t seemed to have been much of an issue over the years for the marketers of garden-variety probiotic formulations, where lumping in a few extra billion CFUs and calling it good seems to be the order of the day. But for higher quality probiotic supplements, it’s an especially pressing question when trying to match the claims on the performance of a particular probiotic formulation with what the science says that particular strain can do. Even the best trained and equipped soldiers won’t be able to achieve much if not enough of them reach the beach.
Capsule suppliers have attacked this two-pronged problem with innovations that both keep the soldiers alive on the ship and deliver them to the shore. In the early history of probiotic supplements, refrigeration was often considered necessary to prevent the premature germination of the organisms on the shelf. This is still a facet of the marketplace, but less and less so as capsule technologies have been developed to create effective moisture barriers, said Missy Lowery, marketing manager of market leader Capsugel. The company has come with solutions to the shelf stability question and have conquered most of the stomach acid issue without having to resort to enteric coatings that, while effective at preventing degradation, can damage probiotics during manufacture because of the high heat involved in their application.
“Capsugel offers a family of capsules for delivery of moisture-sensitive probiotics. The dosage solutions have included innovative polymers for hard capsule products that protect ingredients better and/or allow for targeted delivery. We have also created capsule-within-capsule technology for timed, targeted release of combination prebiotic/probiotic ingredients that also incorporates low-moisture capsules and suspension solutions,” Lowery said.
Chief among these recent innovations has been Capsugel’s line called DRCaps, introduced in 2010. A key part of this innovation is the material from which they’re made. The product is made of low-moisture of hydroxypropyl methycellulose (HPMC) -- with 4 to 6% moisture content at 50% relative humidity (compared to 12 to 14% for gelatin) which according to the company provides better shelf stability and slower disintegration in the stomach, meaning more of the probiotics make it into the small intestine.
Lowery said Capsugel has data gathered in 2013 in an in vivo study using a a radio labeling technique that shows that the capsules last more than 50 minutes before starting to disintegrate, allowing them to dump most of their payload where it counts most.
“The capsules completely released the ingredients in a mean time of 72 minutes after ingestion and when most of the ingredients would most likely be in the intestines,” she said.
Lowery said the company also has solutions for customers seeking to delivery probiotics with another ingredient, such as a prebiotic. Cap-within-a-cap technology, called PrePro Combo, puts a lactobacillus strain in the inner capsule and a FOS suspended in a low-water activity solution surrounding it in the outer capsule. The system delays the release of the probiotic and delivers it to the small intestine with some of the specific food it needs to grow, Lowery said.
“In 2012, Aché, a leading over-the-counter company in Brazil, launched Prolive, a prebiotic-probiotic product delivered via our PrePro Combo capsule-within-a-capsule technology. Today, Prolive is the No. 1 probiotics product in Brazil,” she said.
Conquering tablet hurdles
A step beyond capsules is the tableting technology developed over the last 15 years by Redmond, Washington-based company Nutraceutix, which both produces probiotic microorganisms and the ways to deliver them into the gut, said CEO Tim Gamble.
“At the beginning, the question was consistency in manufacturing. We’ve got that figured out. But we got pulled downstream by our customers asking what makes a really good probiotic. They were asking us for ways to get them past the stomach better than a drink mix or even what a capsule could do,” he said.
Gamble said the first step was a microencapsulation technology called LiveBac, which Nutraceutix developed years ago to solve the stability hurdles and could improve the release characteristics of capsules (which Nutraceutix will also provide to its customers).
“We still do capsules, but there are caveats on them for our customers in terms of their release characteristics,” Gamble said.
“The next step was a pharmaceutical grade delivery technology and we acquired the rights to that from an academic researcher. That is what has now become Bio-tract. It’s a patented tableting technology that protects the probiotic organisms with a controlled extended release that is modifiable by formulation. We can control the release to place lactobacillus strains high up in the intestinal tract and bifidobacteria farther down into the intestine,” he said.
Cysts to the rescue
Another approach to probiotic delivery is to let nature do the work by employing one of several spore-forming strains of Bacillus coagulans, a microorganism that creates a hard cyst in its dormant state. The cysts have specific germination criteria in terms of temperature, humidity and pH, meaning the organism can be used in a variety food matrices as well as being put into a capsule without worrying much about whether the capsule makes it very far into the stomach before spilling its contents. Probiotics in this category are supplied by Ganeden Biotech, Sabinsa Corp. and Nebraska Cultures, and Deerland Enzymes, which supplies a strain of Bacillus subtilis, another spore-forming organism.
Educating the market
While the benefits of certain strains of probiotics are starting the become known among retail buyers and end consumers, the differences between delivery systems is still something of a black box. There seems to be plenty of opportunity for communicating that message to the market. Consumers, and to some extent buyers, are still wowed by big CFU counts, without delving deeper into how those are affected by different delivery modes.
“It’s kind of a complex issue,” said Jon Clinthorn, PhD, senior nutrition education specialist for Natural Grocers by Vitamin Cottage. “We teach a probiotics class at our store for our associates and we delved into into which probiotics are good at supporting which part of the body. We talked about individual strains and how one strain might do something that another strain will not. But everybody seems to have their own delivery system, and we didn’t touch on that as much.”