Once a consumer or practitioner decides which probiotic strain may benefit a specific health target, they must choose from a vast array of formats such as pills, capsules, powders, gummies, suppositories and liquids.
Note: Fermented foods and beverages such as yogurt, sauerkraut, kefir, and kombucha are more difficult to assess quantitatively as a probiotic for two reasons: strains are not always identified on labels and the number of colony forming units (CFUs) are usually not included. The types and dosages may not be clearly stated, making targeting based on clinical studies difficult if not impossible. A future IPA blog will explore how foods and beverages can fit into the big picture.
For now, we will look at what is known about different probiotic supplement modes of delivery.
Manufacturing probiotic supplements, in brief
Many decisions and processes are involved in taking a probiotic strain from the lab to an industrial production. Because probiotics are live microorganisms, production can be challenging as they must remain viable in sufficient amounts until the end of the shelf life or “use by” date. Usually, we can consider that there are several challenges for a manufacturer that produces viable, concentrated stable cells with a high yield. Moreover, a production process must be pursued which is repeatable and easy to apply and follow with all the manufacturing as well as handling and storage processes adhering to strict quality standards.
A 2019 article which appeared in Microorganisms journal titled The Production and Delivery of Probiotics: A Review of a Practical Approach offers an excellent overview of manufacturing and delivery methods.
The first stage of manufacturing involves the inoculation of the growth medium. This requires the formulation of an optimal medium with food-grade components and potentially considering the absence of common allergens. Viable seed stocks of the strain must be available to guarantee genetic stability and consistent quality. After culturing, the microbes are separated from the growth medium and cryoprotectants and lyoprotectants are added to stabilize (e.g. freeze-drying). Finally, cells are blended with excipients (e.g. bulking agents) and flow aids. Other active ingredients may be added to optimize viability, stability, metabolic activity and gastrointestinal (GI) survivability of the microbial cells.
- Viability: ability of organisms to be capable of performing all of the functions necessary for survival, i.e., the continuing existence of the species.
- Stability: The quality of maintaining a constant character in the presence of forces that threatens to disturb it or resistance to change.
- Metabolic activity: Damaged cells may be metabolically active —producing lactase or interacting with immune systems for example —but are unable to multiply hence will not contribute to CFU count. On the other hand, dormant cells are still included in the CFU count but aren’t active. Such cells may be resuscitated; freeze-dried cells are dormant but will be reactivated when in contact with water. One way of assessing activity is measuring metabolic end products; one example is lactic acid in the case of commonly used probiotics.
- GI survivability: Sensitivity of specific strains to harsh stomach acids, digestive enzymes and bile must be considered.
The final product then undergoes packing, storage, handling and other supply chain demands. Environmental factors, temperature, pH, and exposure to oxygen and moisture must be controlled. The main factors impacting stability of freeze-dried probiotics through processing, handling and storage are exposure to water or humidity and storage temperature; these must be strictly controlled.
All these factors must be considered before the product even reaches the beginning of shelf life in a local store. Yet strict quality standards require that the number of live cells must match the CFU count promised on the label until the end of shelf life (stability).
Probiotic delivery formats
Choosing the mode of delivery for a new probiotic being brought to market is one of the most important decisions a company has to make.
In the aforementioned article The Production and Delivery of Probiotics: A Review of a Practical Approach, the authors state, “The inclusion of probiotics in dietary supplements primarily utilizes probiotics in the freeze-dried powder format. Capsules, tablets, and powder in stick packaging or sachets are the most commonly found formats on store shelves and are usually stored at ambient conditions.”
This convenient form of delivery generally increases the stability and shelf life of a product. The probiotic bacteria are entrapped in the tablet matrix, which may protect them against the environmental factors in the human body. However, compression during tableting can damage the cells, leading to a loss of viability and a failure of the therapy. The extent will depend on the formulation, the level of compression and probiotic strain.
Chewable tablets are increasingly popular. They can be a more convenient format for children and others who have difficulty swallowing pills. However, added active ingredients to chewables may be harmful to probiotic survival through increased exposure to moisture (low moisture aids in survival) and negative impact on the freeze-dried probiotics upon rehydration after ingestion. These detriments can be minimized with careful choice of additives and protective packaging.
One more consideration is that plant-derived ingredients may be rich in polyphenols, which may have antimicrobial activity that could harm the probiotic bacteria. For example, one children’s chewable tablet lists these ingredients, some of which may contain polyphenols:
Xylitol, cellulose, stearic acid (vegetable source), natural raspberry flavor, magnesium stearate (vegetable source), glycerin fatty acid esters (vegetable source), beet powder (for color), silicon dioxide, monk fruit extract and citric acid.
Notably, the public is increasingly seeking probiotic supplements free of a long list of additives: animal products, wheat, gluten, soybeans, dairy, egg, fish, shellfish, peanuts, tree nuts and genetically modified organisms (GMOs). Consumers should consult a dietitian or doctor if there are questions or concerns about these ingredients.
Capsules (Regular & Enteric Coated)
Enteric-coated capsules protect the probiotics as they travel through the harsh upper gastrointestinal tract. Studies have shown that probiotics delivered in enteric-coated capsules have higher survival rates compared to non-enteric coated capsules.
Another delivery method is in powder form. However, a study on one strain observed that bacterial stability was greater in tablets than in powders while another study reported that only one of six powdered probiotic strains had excellent GI survival.
Gummies and confectionary have relatively high moisture content; this is detrimental for ‘traditional’ probiotics such as lactobacilli and bifidobacteria. Such products also tend to be hygroscopic further complicating the matter. Gummies therefore often contain spore formers.
However, these sweet treats are popular not only with children but with adults who like a little sugar with their supplements. Not surprisingly, most gummy products list some iteration of sugar as an ingredient, which is devoid of nutritional value except for calories. Corn syrup and other sugars contribute to obesity, diabetes, and tooth decay). Sugar-free options are available. Lest the gummies be viewed as candy, some bottles are equipped with a child-lock.
Suppositories as a dosage form are used primarily for women to deliver probiotics directly to the vagina. Studies show appropriate probiotics may restore and maintain a healthy vaginal microbiome.
While many beverages incorporate or claim probiotic content, for this review of the supplement category, drops are the relevant forms of liquid probiotics. They may be advantageous for children, pets and adults with swallowing issues. Possible refrigeration needs and handling methods may make them less convenient.
Fortunately, consumers have many choices in probiotic supplement formats. Each option offers specific features that may be preferable.
While much is known about each format, there is scant research comparing them. Consumers must do their homework. As always, choosing the right supplement begins with selecting the appropriate probiotic strains that are clinically proven to target personal health concerns.
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Wang, Ziyue et al. “Probiotics for the Treatment of Bacterial Vaginosis: A Meta-Analysis.” International journal of environmental research and public health vol. 16,20 3859. 12 Oct. 2019, doi:10.3390/ijerph16203859