Several years ago, health insurance claims reviewers noticed that a certain animal feed manufacturing company in Cedar Rapids, IA, had unusually low healthcare expenditures. The company had only recently begun self-insuring, and its year-to-year healthcare spending was far lower than actuarial estimates.
How was it possible, the reviewers wondered, that at a time when claims and premium prices were soaring for just about every corporation in the nation, did this company manage to keep its claims rates so very low? Their actuarial curiosity ultimately led to the emergence of a new nutraceutical ingredient that has a host of beneficial immunomodulatory effects.
The feed company’s executives surmised that the overall health of their work force might be related to a proprietary yeast fermentation product, which was a key ingredient in the company’s animal feeds for decades. The substance, produced by Saccharomyces cerevisiae (baker’s yeast), promoted the health, survival, and fecundity of many kinds of livestock.
The company’s leadership knew that their employees, especially those who worked directly in the production of this product, averaged far fewer sick-days compared to many other corporations. They began to consider the possibility that they might have a powerful human immune-system builder on their hands.
From Farm to Pharmacy
Known as EpiCor, the substance was originally developed more than 50 years ago by an Iowa farmer who discovered a way to use S. cerevisiae to produce a fortifying nutrient that seemed to improve the health of his animals. Diamond V Mills, the Cedar Rapids feed company, has been producing EpiCor commercially as a fortifier for animal feeds for decades.
EpiCor is not a yeast extract, but a fermented whole food product containing very high levels of antimicrobial, antioxidant, and immunomodulatory compounds. Prompted by the actuarial inquiry, executives at Embria Health Sciences, Diamond V’s human nutrition subsidiary, sought a consultation from Alexander Schauss, Ph.D., and his research team from the American Institute of Biosocial and Medical Research (AIBMR), a life sciences lab specializing in analysis of nutritional ingredients, with a particular focus on immunology.
Dr. Schauss and his team began by doing thorough immunologic assessments on blood samples from 10 workers directly involved in production of EpiCor, as well as from 10 age- and gender-matched employees working in non-production positions. They found several significant differences.
Enhanced NK Activity, Increased IgA
Compared with the controls, the exposed workers showed a markedly lower number of CD8 T-suppressor cells, which corresponded to a significantly higher CD4 (T-helper)/CD8 ratio, indicating better first-line immunity against pathogens. They also had higher levels of natural killer (NK) cell activity and increased NK cell cytotoxicity, despite overall lower NK cell counts. The exposed workers had much higher total salivary IgA levels, but lower levels of circulating specific immune complexes, and increased levels of glutathione in their red blood cells.
Chris Meletis, ND, former Dean of the National College of Naturopathic Medicine, has been following EpiCor’s development from these early stages. He noted that he was particularly impressed with the increased salivary IgA levels seen in people exposed to the substance, viewing it as, “the equivalent of an immunological envelope protecting … all the places where pathogens can enter the system.”
Dr. Schauss said EpiCor seemed to be inducing, “an enhanced adaptive immune response … and an optimally functioning innate (humoral) immunity.” The humoral immune response is the body’s generalized, non-specific response to environmental pathogens. This could account in large part for the low levels of sickness among Embria employees as a whole.
Based on these findings, Dr. Schauss undertook a full-scale investigation into the immunomodulatory properties of EpiCor. He presented his findings in an online press conference this summer.
A Micronutrient Cornucopia
EpiCor contains very high levels of antioxidants, with ORAC values far in excess of those obtained for blueberries and other antioxidant rich foods. A 500 mg dose of EpiCor includes almost 15 mg of catechin, the primary antioxidant in green tea, as well as other antioxidants like resorcinol and trans-resveretrol. Even at very low doses of 1 part per trillion, EpiCor is able to inhibit formation of reactive oxygen species (ROS) in vitro. “It works as an antioxidant at physiological cellular levels.”
The substance also contains high levels of β-glucans, which are the immunomodulatory cell-wall compounds that give medicinal mushrooms like Maitake and Reishi their immune system enhancing properties. EpiCor also contains glucans and mannan oligosaccharides that are not found in mushrooms or yeast extracts.
It contains large amounts of protein (150 mg per 500 mg dose), soluble (69 mg per 500 mg) and insoluble fiber (81.5 mg per 500 mg), a full complement of B vitamins, important minerals like calcium, magnesium, potassium and phosphorus, and phytosterols including ergosterol (a vitamin D2 precursor).
After determining that there is, indeed, cause to believe EpiCor enhances human humoral immunity, Dr. Schauss tested the compound against a number of common human bacterial and fungal pathogens including Escherichia coli, Staphylococcus aureus, Candida tropicalis, and various coliform bacteria. He found that even at very low concentrations, it could inhibit growth of these pathogens, particularly E. coli. Though it remains to be tested in human subjects, he suggested it might have a “prebiotic” effect in the gut, promoting the growth of healthy gut flora while inhibiting pathogens.
As part of a stability testing protocol, he inoculated samples of EpiCor with Salmonella, S. aureus and a number of different molds and found that the substrate quickly diminished the number of retrievable organisms, again suggesting a direct antimicrobial effect.
No Effects on CYP450
As Embria began laying plans to develop EpiCor as an ingredient for the human dietary supplement market, they began to consider the issue of supplement–drug interactions. “Given that roughly 42% of all US adults are on medications of some sort, we wanted to see if this product would affect drug metabolism,” said Dr. Schauss. Using immortalized human hepatocyte assays and protocols used in pharmaceutical development, he assessed the impact of EpiCor on the cytochrome P450 enzyme system.
The good news is that EpiCor has no effect on any of the CYP450 enzymes, an indication that it will not interfere with drug metabolism. Dr. Schauss also conducted month-long pharmacokinetics studies in 15 men and women, who took 500 mg EpiCor per day. The subjects were also given single doses of dextromethorphan and alprazolam, which are known to be metabolized by specific CYP450 enzymes. EpiCor had no effect on drug metabolism.
Dr. Schauss’ team has run multiple immune system analyses on people taking EpiCor, 500 mg daily. They recently published data in the Journal of the Federation of American Societies of Experimental Biology (FASEB) summarizing some of the findings (Schauss A, Vodjani A. FASEB J. 2006; 20(4): A143), and are preparing 4 papers for publication in peer-reviewed journals.
Reducing Inflammation, Improving Cell Signaling
Several findings stand out. EpiCor consistently activates NK cells, which, when taken from test subjects and tried against a variety of human tumor cell lines, showed strong cytotoxic activity. Given that NK cells are the body’s first line of defense against bacterial and viral pathogens, as well as prime players in eliminating aberrant cells, EpiCor could potentially increase an individual’s resistance to a wide range of infections and, possibly, malignancies.
It also down-regulates phytohemagglutinin-triggered production of interferon-γ. “The significant inhibition of IFN-γ production indicates that EpiCor also has anti-inflammatory properties.” Overall, the in vitro data show that it can quell systemic inflammation, suggesting this product might have a role in the treatment of a host of autoimmune inflammatory diseases, particularly gastrointestinal conditions like irritable bowel syndrome and Crohn’s disease.
Moreover, EpiCor induces calcium signaling between various types of immune cells, a key process in mounting coordinated immune responses. It also positively affects expression of adhesion molecules on the surfaces of T-cells, B-cells and dendritic cells.
Studies of humans taking the substance daily corroborated the initial findings of increased salivary IgA in the Embria plant workers. “This is very important because if you can keep pathogens out of the bloodstream (via IgA mediated immunity), you increase the immune system’s ability to deal with other issues like eliminating mutated precancerous cells.”
In June, an expert panel review by leading toxicologists affirmed EpiCor’s status as “Generally Regarded As Safe” (GRAS), allowing it to be incorporated into nutritional supplements and foods. A human formulation of EpiCor was recently introduced to the US nutraceutical market by Vitamin Research Products (www.vrp.com), a practitioner-only line of nutritional products.
VRP is positioning EpiCor primarily as an “immunogen,” a non-toxic immune-system builder that can help people avoid common infectious conditions such as colds, flu and respiratory infections. According to Dr. Schauss, the product is not so much a treatment for these conditions once they’ve taken hold, as it is an ongoing preventive therapy.
It may have clinical applications well beyond the prevention of common infections, including the management of autoimmune diseases, but research in these directions has not yet begun. Dr. Schauss said, though, that several clinical trials involving EpiCor are now in the planning stages. “This is one of the most promising agents I have seen, ” said Dr. Meletis.
