Probiotics and digestive enzymes are two critical components providing microbiome health solutions. Both contribute differently to microbiome health. As with any other dietary supplement, supply chain is vital, ingredient source is critical, and many manufacturers are buying ingredients that are not adequately vetted.

If you do not put good quality in, you cannot get good quality out. Unlike most dietary supplement ingredients, probiotics and digestive enzymes are not single ingredients; rather, they represent categories of different strains that offer varying benefits. This means that manufacturing, formulation, and packaging requirements are different than for most dietary supplements.

Probiotics & Process
For probiotics specifically, testing products to ensure they remain stable and potent throughout shelf life is also complicated and can be inconsistent, contributing to quality challenges.

Making a probiotic product takes significant expertise, starting with raw material procurement, production environment, quality control processes, equipment used, testing along the way, and storage capacities, all the way through to finished product—it is all connected. If one step gets overlooked, it could impact the entire production. The manufacturing process for finished format probiotics in two-piece capsules is one of the most influential factors for a product’s potency, effectiveness, and value. It starts with quality and potency of strains at the beginning of the process and finishes with final consumer packaging.

Many emerging studies are touting the health benefits of probiotics, but they also exemplify the industry’s tendency to jump out ahead of the science. New science has now expanded the relevance of probiotics beyond gut health, with evidence demonstrating their importance for pain, immunity, mood, and cognition. And there is ongoing investigation into how specific strains affect individual conditions. The most extensively studied probiotic species include Lactobacillus, Bifidobacterium, Saccharomyces, Streptococcus, Enterococcus, and Bacillus, among others.

One probiotic strain is not equal to another. There are significant differences between strains and their benefits, which also impact their stability and performance in a product. With the growing demand for more probiotic products, there has been a race among manufacturers to add more strains and colony forming unit (CFU) counts to products to differentiate them in the market. Companies may say their product has a blend of 10 strains and 30 billion CFUs, while only one or two strains are doing the heavy lifting. The rest of the strains are just there in small amounts to window-dress the formula and make the label look impressive. A growing number of brands and consumers address this issue by requiring labeling of amounts of individual probiotic strains rather than simply stating the total.

Targeting Delivery
The goal of producing finished format probiotics is to keep the strains dormant until they reach the targeted area in the body, at which time they activate and go to work. Achieving this goal is an imperative in maintaining stability. The foundation for success is the quality and potency of the strain, but proper handling of the microbes is equally essential. If a facility does not have appropriate air handling systems and controls for temperature and humidity in place, the likelihood of product stability is decreased.

As for enzymes, many people take them in the form of dietary supplements to replace the enzymes their body is lacking, or to fortify the enzymes found in their food to ensure complete digestion of each meal. If you do not digest the food, you cannot absorb the nutrients. And if you do not absorb the nutrients, you cannot get all the fuel you need for repair, growth, and learning.

It has been estimated that the human body consists of about 10 trillion cells and 10 times as many microorganisms inhabit each of our intestines. These organisms support regularity, aid the immune system, produce vitamins like B and K, and fuel digestion through their production of enzymes, including lactase, protease, and amylase. Each of us has a unique ecosystem in our digestive tract, and it appears to be influenced by genetics and diet. Enzymes work to break up and facilitate efficient digestion of food. Just like most things in life, the key is to be balanced.

Encapsulating enzymes requires extra precaution and personal protective equipment because digestive enzymes work outside the body as efficiently as inside the body. If your skin or air passages encounter digestive enzymes, the result will be a burning appearance or feeling. Some manufacturers with less than effective air handling systems report office workers complaining about the effects of inhaling digestive enzymes that have escaped into the air. Air handling is critical.

Controlling the Process
While manufacturing, stability, and quality requirements for these microbiome products are vastly different, they are still all regulated and produced under the same good manufacturing practices (GMPs) required under the Dietary Supplement Health and Education Act (DSHEA). A formula manufactured with price as a primary concern may lead to a low price point but will be missing key ingredient and manufacturing safeguards which give the product efficacy months to years past the stated term at date of manufacture.

Both probiotics and digestive enzymes require specialization in both production and packaging to ensure the products remain as effective at the time of manufacture as they are at the time of ingestion. There are several critical components manufacturers must provide to create effective digestive health products involving probiotics and digestive enzymes:

Overages: Almost every ingredient requires an inclusion of overage to meet expiration date. The less stable the ingredient the more likely the necessity of a substantial overage requirement. Few ingredients are less stable than probiotics. Even different strains of probiotics have different stability profiles. Interactions among various strains of probiotics as well as interactions between other ingredients or excipients can impact the life of the probiotic. It is important to note that simply meeting label claim at time of production ensures a sub-performing probiotic at ingestion.

It is not unusual to manufacture a product with 300% of label claim at manufacturing date. This amount is sometimes required to meet a two-year expiration date. Consider the human body is estimated to contain 40 trillion CFU bacterial cells and other microscopic organisms, known as the microbiome (Sender R, et al. PLoS Biol 14(8): e1002533). Most retail brands offer supplements with a label claim of 1-10 billion CFU. While 10 billion CFU might sound like a high number to begin with, compared to the 40 trillion CFU in our body, it really isn’t. The probiotics we use as supplements are specifically tested and found to be beneficial to specific outcomes.

Formulation: While many dietary supplement ingredients are straightforward, probiotics are not. Probiotics require precision. Clinical efficacy is significant, and potencies vary from one ingredient to another. It is not just about the ingredient as it comes in the door. There are multiple layers to the formulation, including ensuring compatibility and viability. Mistakes and oversights in a formulation can be costly, so it is imperative to have experience when formulating with these ingredients. The product needs to meet both stability requirements and label claim, which requires calculations on exactly how much active ingredient needs to be added.

Quality Ingredients: All ingredients should be tested to ensure identity, strength, composition, quality, and purity throughout the manufacturing process. Quality is a leading factor for success in supplement manufacturing, but especially in probiotics. It starts with using the best ingredients from vetted and qualified suppliers who a manufacturer works with regularly. Manufacturers should test at every step of the production process to ensure viability of the ingredients.

Environmental Controls: Probiotics and enzymes are both susceptible to the environment, so manufacturers must handle them carefully throughout the manufacturing process. Experts advise the entire production facility, not just the encapsulation areas, should maintain a relative humidity of 20% and a temperature no greater than 68°F.

Cold Storage: Cold storage of probiotic materials is important to implement as much as possible, from receipt of the ingredient to the final products’ shipping. It is essential to store probiotics in cool temperatures until they are needed for manufacturing. The refrigerated microbes should never be exposed to the ambient 68° manufacturing environment until they are fully tempered to the proper ambient condition. It is also essential to maintain 20% humidity to protect the probiotics’ quality and ensure they are not drawing moisture or increasing water activity during manufacturing.

Packaging: Producing a probiotic or digestive enzyme that is not protected post-production can lead to products that become ineffective before ingestion. While many still use standard plastic or glass bottles, blister packs are now seen as a cutting-edge method for protective packaging. The pharmaceutical community has employed this technology for years, but now the cost of packaging blister packs is almost identical to bottling in plastic. Aluminum-Aluminum blister packs offer a moisture and oxygen barrier that provides a protective cavity, increasing shelf life and adding stabilizing protection for probiotics—maintaining the 20% humidity.

Science: Probiotic science is continuing to explode, providing new clinical research expanding our understanding of relationships beyond gut health. For example, the Harvard Health Publishing division of Harvard Medical School recently updated its list of potential probiotic benefits, which includes items like irritable bowel syndrome, Crohn’s disease, vaginal infections, H. pylori (which causes ulcers), eczema in children and more.

In addition to expanded benefits of probiotic strains, emerging science supports the advantages of prebiotics. Every living microorganism needs to eat. Probiotics are living microorganisms that feed on prebiotics.

Prebiotics are non-digestible dietary fibers that serve as food for probiotics. Prebiotics can enhance the metabolic activity and growth of beneficial bacteria. When combined, probiotics and prebiotics may have synergistic effects.

Both enzyme and probiotic supplements can help with GI health. Enzymes enhance the digestion of foods, while probiotics help support the immune functions of the gut. While enzymes and probiotics support gut health, each needs the other for the gut to function optimally.

Building Trust, Sharing Transparency
Suppliers, retailers and industry owe it to our consumers to provide detailed, ongoing and accurate information supporting probiotics and digestive enzymes. Information and education should support not only the clinically proven benefits of probiotics and digestive enzymes, but also the complexities and importance of responsible production and packaging.

Today’s consumers are becoming increasingly aware of the benefits of probiotics and digestive enzymes. Knowledge of the impact of the microbiome on holistic health is also increasing. Consumers are combining awareness of the benefits of enzymes and probiotics and becoming more discerning as to the importance of quality manufacturing in ensuring quality products.