Scientific Analysis

A Unique Immune Enhancing Dietary

Supplement Ingredient: EpiCor

By Alex Schauss

A company in Cedar Rapids, Iowa, that produces fermentation products discovered that a large group of employees working in one of the fermentation facilities that made a fermentate had an unusually low incidence of sick leave over many years.

A careful examination of health care costs led to the discovery that these employee’s annual health care expenses was extraordinarily low compared to other employees working in offices or other jobs for the company. Interviews with these plant employees determined that although many of the employee’s families had seasonal illnesses, the employees working in the plant seemed immune from them.

To see if there was some scientific evidence to support the discovery, a study was carried out to assess the immune systems of “exposed” and “non-exposed” employees that worked for the same company, who lived in the same community, matched for gender, age, and years of employment. Twenty volunteers were chosen to participate, each of whom provided blood and saliva samples. The samples were sent to a laboratory in Los Angeles that specializes in measuring immunological markers in humans.

The results were quite surprising. Compared with the controls, the exposed workers showed markedly lower numbers of T-suppressor cells, which corresponded to a significantly higher T-helper to T-suppressor ratio, indicating an enhanced first-line immunity against pathogens. The exposed workers also were found to have higher levels of natural killer (NK) cell activity and increased NK cell cytotoxicity (ability to kill viruses, bacteria, and cancer cells, despite less NK cells. This suggested that their NK cells were more efficient. The exposed workers also averaged much higher salivary IgA levels than non-exposed employees, yet had lower levels of circulating specific immune complexes, in addition to increased levels of glutathione in red blood cells.

The high IgA levels were of particular interest, as these levels were interpreted by several specialists in immunology as the equivalent of an immunological envelope capable of protecting individuals from pathogens entering their bodies. Based on these initial differences between exposed and non-exposed employees, the company requested that studies be carried out on the fermentation product to determine its safety, mode of action, and pharmacokinetics.

Early studies involved a full characterization of the fermentate (later to be concentrated under food good manufacturing practices (GMPs) and sold as a dietary supplement ingredient called “EpiCor”). A surprising number of compounds were found in EpiCor known for enhancing innate immunity. To find so many in one ingredient was a surprise. For example, it contained catechins found in green tea, as well as resorcinol and trans-resveratrol, found in grapes.

High levels of some compounds, such as squalene, with known immune enhancing properties, were unexpected, as were compounds known to support the brain and the CNS, including phosphotidylserine, phosphatidylethanolamine, phosphatidylglycerol, and phosphotidylmyoinositol, along with a complement of plant sterols, such as ergosterol (a vitamin D-2 precursor), zymosterol, and episterol. In addition, the fatty acid profile of EpiCor was nearly ideally suited for humans, with monounsaturated and polyunsaturated fatty acids predominating. The fermentate had a comprehensive complement of essential vitamins, minerals and trace elements, amino acids (300 mg per gram), yet its heavy metal levels were at a fraction of a part per billion, which is extremely low (based on ICP/MS analysis) for anything in this polluted world we live in. A test for residues of pesticides or insecticides, using US FDA and USP analytical panels, found no detectable levels for any of over 160 compounds tested.

EpiCor was found to contain high levels of beta-glucans, which are known immunomodulatory cell wall compounds that give medicinal mushrooms such as the Reishi mushroom some of its immune enhancing properties. Interestingly, EpiCor had high levels of mannan oliosaccharides (MOS), not found in yeast extracts. MOS binds to certain pathogenic microorganisms preventing colonization of the gut. Additionally, MOS can activate the complement system via the lectin activation pathway, further protecting the gut from invading pathogens. As the fermentate contained compounds normally found in food, the question was raised as to whether or not it had any antioxidant activity. A sample of EpiCor was sent coded, so lab personal would not know what they were testing, to the leading antioxidant lab in the world to perform a series of oxygen radical absorbance capacity (ORAC) assays to see whether it scavenged the peroxyl, hydroxyl, peroxynitrite, and superoxide radicals.

Again, the results were completely unexpected. Not only did it scavenge these radicals but the total lipophilic and hydrophilic peroxyl scavenging activity as measured by ORAC exceeded 500 micrograms Trolox equivalents (TE) per gram, higher than all but a few foods known to have antioxidant activity tested by the United States Department of Agriculture (USDA). Repeat testing of non-sequential lots continued to show the same results. EpiCor’s activity against a number of bacterial and fungal pathogens, including: Staphylococcus aureus, Escherichia coli, and Candida tropicalis was also tested. Again, the results were surprising. EpiCor showed total inhibition at dilutions down to one part per trillion for C. tropicalis and S. aureus, and one part per million for E. coli.

This led to the suspicion that EpiCor has an effect in maintaining a more desirable ratio of gut bacteria, with the consequent enhancement in production of secondary metabolites by “good” bacteria that benefit human health. As it became clear that the company would introduce the improved version of the fermentate (EpiCor) as a dietary supplement for humans, a series of animal toxicology studies was commissioned. The two weeks Limit Test (acute toxicity test) showed no mortality or adverse effects in any animal at a dose of 2,000 mg/kilogram of body weight (BW). A 90-day subchronic toxicity study at doses up to 1,500 mg/k BW per day also showed no adverse effect nor any evidence of any morphological changes in animals based on extensive histopathological examination in 160 animals given high doses of EpiCor daily for the human equivalent period of 1.5 years. This study established a no observed adverse event level (NOAEL) for EpiCor of 1,500 mg/kg of body weight. As more than 40% of adults in the United States are taking prescription medications, it seemed prudent to determine if EpiCor would result in any drug interactions with commonly prescribed prescription drugs or OTC’s.

The first study used immortalized human hepatocytes in an in vitro protocol drug companies use to determine if an agent might effect the cytochrome P450 enzyme system, which is involved in drug metabolism. One wants to see if EpiCor interferes with the liver’s metabolism of such drugs. EpiCor did not affect any of the CYP450 enzymes, an indication it would not interfere with drug metabolism. As a follow-up, a month long human pharmacokinetic study was carried out in 15 healthy men and women, who consumed 500 mg of EpiCor per day. During the study subjects were given single doses of drugs known to metabolize specific P450 enzymes. EpiCor had no effect on drug metabolism, but it did have an effect on immune parameters – they all improved, particularly salivary IgA and NK cells and NK activity. EpiCor was also studied for mitogenicity and mutagenicity. Bioassays using human cells found no evidence of mitogenicity. Both the bacterial reverse mutagenicity assay (AMES test), and the mammalian cell gene mutation test in mouse lymphoma L5178-Y cells, was negative, meaning that EpiCor was found not to be mutagenic.

Stability and microbiological studies showed EpiCor to be stable at room temperature and humidity based in a two-year shelf-life study. Even when inoculated, using a standard microbiology protocol that inoculated EpiCor with various pathogens, the results showed lower pathogen count after 30 days (below 10 CFU/g). Mode of action research, to study how EpiCor works, has proven particularly interesting. Innate defenses act within hours of a pathogen’s appearance in the body and are nonspecific in that they target any pathogen. This defense system includes the skin, which excludes pathogens from entering the body, the cilia in mucous membranes, which remove airborne dust and pathogens, nasal secretions, saliva, and tears, which each contain pathogen destroying enzymes.

Additionally, a host of internal defense systems involving phagocytic cells, called neutrophils, dendritic cells (particularly rich in our skin and mucus membranes), and macrophages kill invading pathogens. So what have some of these studies demonstrated in terms of how EpiCor works? In one study, EpiCor was assessed by using a model that pre-incubates human immune cell subsets in vitro with and without EpiCor to produce radical oxygen species (ROS) formation following exposure to hydrogen peroxide. The results of this study found a statistically significant reduction in ROS formation at extreme dilutions, finally terminating at 0.01 parts per trillion. EpiCor also induced calcium signaling in human NK and B lymphocytes.

Signaling is pivotal to the coordinated response of cells in tissues and organs within the whole body. It is now well established that cells do not behave as selfish entities but rather tend to form “micro-societies” whose proper functioning requires a precise coordination of emission and reception of signals. Dysfunction of the networks is associated with pathological. This is why the finding that EpiCor facilitates calcium signaling between cells is important, for it may explain in part how it enhances immune response to invasive pathogens. Much more has been learned about its ability to modulate the immune system over the last few years. This has led to the suggestion that this fermentate is a high metabolite immunogen, as reported in late 2006 at an international anti-aging conference. EpiCor’s safety as an ingredient was affirmed by an expert panel of toxicologists who declared it “Generally Recognized As Safe” (GRAS) based on the scientific evidence for its safety when added to foods at the recommended daily dose. The recommended dose of EpiCor based on research is 500 mg a day. One capsule containing 500 mg of EpiCor would provide this amount in a single dose taken with food and sold as a dietary supplement.

References

Schauss AG, Vodjani A. Discovery of an edible fermentation product with unusual immune enhancing properties in humans. Federation of Societies for Experimental Biology Journal, 2006; 20(4): A143.

Schauss AG, Jensen G, Vojdani A, Financsek I. The discovery of a yeast fermentate with unexpected significant immune modulatory activity when consumed by humans. Journal of the American College of Nutrition, 2006; 25(5): 465.