Intuitively, people have been eating healthy, fermented foods for thousands of years. As the natural health products market has grown in technological innovation and research, fermentation- based supplements have earned their place in promoting human health and wellness.

The (Not-So) Basics 

In its simplest form, explained Hartley Pond, vice president of technical sales with California-based FutureCeuticals, Inc., fermentation is nature’s process of breaking down food. Normally, predigestion occurs in the gut, which makes foods more bio-available to the body. Healthy bacteria starts the fermentation process prior to ingestion, contributing to the body’s ability to readily utilize the available nutrients in food.

“Fermentation is a metabolic process in which an organism, such as a microbe, is used to convert a carbohydrate, like starch or sugar, into alcohol or an acid,” elaborated Ronald Marzoli, vice president of marketing and sales with Daiwa Health Development in California. Depending on the substance formed, the process is called alcohol fermentation, lactic acid fermentation or amino acid fermentation, etc. Conversely, if a microbe breaks down a material and the result is toxic or holds no benefit, the process is called putrefaction.

Humans began tinkering with fermentation in the lab in the 19th century, explained Vladimir Badmaev, MD, PhD, head of R&D with NattoPharma ASA in Norway. Although Louis Pasteur showed that fermentation is a result of the action of living microorganisms, he could not explain its basic nature. In 1860, he demonstrated that bacteria causes milk to sour, and his work in identifying the role of microorganisms in food spoilage led to the process of pasteurization.

However, Pasteur was unsuccessful in attempts to extract the compounds from yeasts responsible for the fermentation process. In 1897, German chemist Eduard Buechner was able to extract a juice from ground up yeasts, and used that liquid to ferment a sugar solution, forming carbon dioxide and alcohol much like living yeasts.

“Buechner concluded that the extract had the same properties as the whole yeasts due to content of ‘ferments’ or enzymes,” said Badmaev. “From that time on, the term ‘enzyme’ has been applied to all ‘ferments.’ The groundbreaking work for which Buechner won the Nobel Prize in chemistry in 1907, provided understanding that fermentation is caused by enzymes that are produced by microorganisms.” 

Currently and in general, elucidated Dr. Mark Wach, vice president and director of research with Pennsylvaniabased Sylvan Inc., “by carefully defining the growing parameters from beginning to end, and manipulating them according to the needs of the product, a dietary supplement can be produced under controlled conditions by a given bacterium, fungus or plant to exacting specifications. This can remove the inherent variation found in products harvested in the wild. It also makes it easier to control for both natural and introduced toxins such as heavy metals and pesticides.” 

Today, fermentation provides a critical role and function in dietary supplements for the consumer. Fermentation, said Daiwa’s Marzoli, can transform a Natural material that has limited or no benefit to humans into a very valuable product for human health. Brand marketers should note that from a production viewpoint, fermentation allows suppliers to inexpensively mass-produce ingredients that, if produced through other more sophisticated processes, would result in higher costs, and the result would be an ingredient that would no longer be considered “natural.” “In addition, the fermentation process may produce a mix of several materials that together provide synergy and even greater benefit then a single ingredient developed with synthetic chemical processes,” he added.

“The fact is that very few of us consume enough ‘live’ foods to contribute to or maintain a healthy microflora,” said FutureCeuticals’ Pond. “Fermentation offers an opportunity to enhance our already healthy dietary supplement ingredients with the benefits of an ancient food preparation technique rooted in delivering active, healthy bugs.” 

Recent Innovations 

Probably the most recognized fermentation- derived dietary supplements are probiotic bacteria, said Badmaev. But the most recent example of fermentation- obtained dietary supplements, he offered, is a natural vitamin K2 especially menaquinone-7 (MK-7), which is emerging through research to show powerful benefit in bone and heart health. The modern fermentationobtained vitamin K2 has been inspired by natto, a widely consumed fermented soybean dish in Japan, considered a rich source of dietary menaquinones, particularly menaquinone-7.

In the past few years, Sylvan’s Wach pointed to improved microprocessor systems, better air control systems, and continual refinement and improvement in the supply of raw materials, which have all helped to improve the fermentation process and product results in terms of efficiency and accuracy.

According to Pond, numerous research teams have investigated the particularity of each probiotic species for certain starches, proteins and simple sugars by the enzymes that they produce. The different species of cultures have different preferred nutrient sources they use as food, and also different waste products as they grow and reproduce. This information can be combined along with the selected fruit and/or vegetable matrix developed to help optimize the end product into a unique, proprietary and rationally designed formula.

Futureceuticals, he added, is now RiboPrinting its probiotic species down to the strain level in order for brand marketers to deliver the precise strains their consumers expect. The primary advantage of RiboPrinting, he explained, “is that it allows us to look at a much larger section of the bacterial genetic makeup. It analyzes not only the 16S section, but also the 5S and the 23S sequences, as well as additional sections of genetic material. We are thus able to differentiate bacteria DNA all the way down to the strain level. This allows us to differentiate between, for example, various strains of Lactobacillus acidophilus. Futureceuticals is also improving its fermentation media by adjusting the growth conditions. Manipulations in temperature, pH, growth media and frequency of growth cycle can be used to improve the viability and concentrations of specific cultures.” 

In the past five years, the team at NattoPharma has striven to improve the quality of vitamin K2 (menaquinone 7) by concentrating on purity, which has led to the development of new fermentation technology providing highly pure MK-7 crystals (MenaQ7 Crystals). Up until this launch, said Badmaev, what was available lacked purity, stability and standardization, causing vast differences in resulting efficacy. Traditional fermentation processes to arrive at MK-7 material often had allergens and contaminants as soy and anti-foaming agents, along with other menaquinones, which may interfere with the gastrointestinal absorption and bioavailability of MK-7 to target tissues (e.g. bone and blood vessels).

Menaquinone-7 is prepared by submerged fermentation using B. licheniformis, a non-toxicogenic and nonpathogenic strain, as the production strain and gram flour (made from chickpeas) and dextrin as carbon and nitrogen sources. The menaquinone-7 in the fermentation broth is then spray dried and is extracted with hexane. The extraction step purifies the oil in an extractor and the excess oil discarded in the cake. This gives pure K2 in the solvent. The solvent is then concentrated by vacuum distillation to a critical mass. At this point K2 crystallizes; it’s filtered, washed and dried. The production procedure assures a consistent and high quality menaquinone-7 product.

“It is a proprietary, multi-step process of purification, condensation and crystallization of fermentationderived K2,” Badmaev explained. “The resulting crystal form of vitamin K2 is a direct outcome of purity of the MK-7 molecule and is a much more desirable outcome for the stability, efficacy and safety of the end product. This innovative process leads to an end product that is more than 95 percent pure natural menaquinone-7 or MK-7 (100 percent- trans form), with less than 0.5 percent (traces) of menaquinone-6 (MK-6), a marker of natural menaquinone-7 technology—by the way, MK-6 is not contained in synthetic versions.” 

Challenges 

Because fermentation is such a unique process with which companies continue to strive to improve products, there have been some challenges along the way.

Fermentation has a long history in Japan, where Daiwa Pharmaceutical of Tokyo (parent company of Daiwa Health Development) has experience with the use of fermentation in making dietary supplement ingredients since the early 1990s. The company’s core fermentation skills lie in anaerobic and aerobic fermentation processes, it covers aerobic culture using Lentinula edodes and Bacillus subtilis natto, and anaerobic culture using Lactobacillus. “So the challenges were to find out the best mix of the Bacillus, medium, temperature, humidity, fermentation period, etc., to produce our ingredients on a commercial scale,” said Marzoli. “There is no shortcut to overcome those challenges—it is done empirically, with many trials and errors.”

Further, “Contamination is really a big challenge for any fermentation process, including ours,” Marzoli added. “In order to overcome this particular challenge, our factory is equipped with several anti-contamination measures as well as being certified with HACCEP and ISO9001 standards.” 

According to Sylvan’s Wach, unique challenges are inherent in solid substrate fermentation. Input raw materials must be sourced to ensure compatibility not only on a nutritional basis, but also from a density and particle size standpoint to ensure adequate mixing and distribution throughout the growing matrix. The substrate matrix must allow adequate water retention while simultaneously permitting sufficient gas exchange to occur.

“Sylvan uses a number of fermentation vessels that allow for varying degrees of evaporation, gas exchange and temperature control to accomplish these tasks, which allows for a very high degree of sophistication and control in the production process, and leads to the manufacture of a superior product,” Wach described. “In addition, we have adapted and developed numerous analytical processes designed to measure a large number of the process parameters unique to solid substrate fermentation, allowing us to closely monitor our current processes and help develop new products.” 

A primary challenge in Pond’s viewpoint is not technical, but more educational. “It’s fighting the idea that all micros are bad, and that food and supplements need to be completely sterile to be safe,” he said. “While eliminating the presence of harmful pathogens is, of course, required, often the conflation between harmful and helpful bacteria and the drive to reduce overall micro-load in food stuffs leads to overprocessing and creating food that is substantially sterile and devoid of live nutrients.”

Although industry innovators are creating new and targeted fermentationbased supplements for health, consumers are just starting to understand the link between “fermentation” and good health, thanks largely to the probiotic arena. This segment could have tremendous potential and exemplify leadership in technology and supplement science.