Antioxidant bioavailability and rapid immune-modulating effects after consumption of a single acute dose of a high-metabolite yeast immunogen: results of a placebo-controlled double-blinded crossover pilot study

Abstract

The objective of this pilot study was to investigate the acute effects on circulating lymphocyte subsets, antioxidant status, and cytokine profile after consumption of EpiCor(®) (EP) (Embria Health Sciences, Ankeny, IA, USA), a dried fermentate produced from Saccharomyces cerevisiae, using a placebo-controlled randomized crossover study design with 12 healthy adult human subjects. EP contains high levels of bioavailable antioxidants and strongly activates natural killer (NK) cells in vitro. EP consumption has been shown to increase erythrocyte hematocrit levels, boost mucosal immune protection, reduce cold/flu symptoms, reduce seasonal allergy symptoms and the need for rescue medication, and increase salivary secretory immunoglobulin A levels. This warranted further study on immune effects in humans. A within-subject analysis of data collected before and at 1 and 2 hours after consumption of a single dose of 500 mg of EP versus placebo was performed. A transient reduction in circulating T and NK cell numbers was observed 2 hours post-consumption, suggesting that homing and recirculation of these cells, as part of healthy immune surveillance, were supported by EP. The increased expression of activation markers on the CD3(-) CD56(+) NK cell population was significant for CD69 at 1 hour post-consumption (CD25, P<.07; CD69, P<.05), whereas for CD25 it was significant at 2 hours after consumption (CD25, P<.03; CD69, P<.15). A rapid increase in serum interferon-γ was observed at 1 hour post-consumption (P<.07; after removal of two outlying data sets, P<.05) and may have contributed to the effects seen on NK and T cell subsets. Significant increase in serum antioxidant protection was seen 2 hours after consumption (P<.04). Thus consumption of a single 500 mg dose of EP provides a rapid and transient effect on the trafficking and activation status of specific lymphocyte subsets, as well as increased antioxidant protection.

FIG. 1.

Diagram outlining the double-blinded placebo-controlled study design. The order in which each subject consumed placebo versus EpiCor was randomized so half the number of subjects received placebo on the first study day, and the other half of the subjects received EpiCor on the first study day.

FIG. 2.

Changes in the number of circulating T cells after consumption of placebo and 500 mg of EpiCor (EP). (A) The group averages are shown for changes seen after consumption of placebo versus EP (mean±SD). (B) The individual changes were compared for each subject to evaluate the change in each subject's response to EP in comparison with the same subject's response to placebo. Using a within-subject analysis, a statistically significant reduction in T cell numbers was seen for EP at 2 hours post-consumption (P<.01), suggesting increased immune surveillance.

FIG. 3.

Changes in NK cell counts after consumption of placebo and 500 mg of EP. (A) The group averages are shown for changes seen after consumption of placebo versus EP (mean±SD). (B) The individual changes were compared for each subject to evaluate the change in each subject's response to EP in comparison with the same subject's response to placebo. Using a within-subject analysis, a statistically significant reduction in NK cell numbers was seen for EP at 2 hours post-consumption (P<.05), suggesting increased trafficking of NK cells.

FIG. 4.

Changes in expression of the CD25 activation marker on CD3⁻CD56⁺ NK cells after consumption of placebo and 500 mg of EP. (A) The group averages are shown for changes seen after consumption of placebo versus EP (mean±SD). (B) The individual changes were compared for each subject to evaluate the change in each subject's response to EP in comparison with the same subject's response to placebo. These data were then analyzed using a within-subject paired t test. The EP-induced increase over placebo was not significant at 1 hour (P<.07) but reached statistical significance at 2 hours (P<.05).

FIG. 5.

Changes in expression of the CD69 activation marker on NK cells after consumption of placebo and 500 mg of EP. (A) The group averages are shown for changes seen after consumption of placebo versus EP (mean±SD). (B) The individual changes were compared for each subject to evaluate the change in each subject's response to EP in comparison with the same subject's response to placebo. These data were then analyzed using a within-subject paired t test. The EP-induced increase over placebo was significant at 1 hour (P<.05), but the statistical significance disappeared at 2 hours (P<.15), indicating a rapid, but transient response.

FIG. 6.

Comparison of Cell-based Antioxidant Protection in Erythrocytes (CAP-e) data on a complex natural product, EP, in vivo. EP consumption provided statistically significant improvement in serum antioxidant capacity, when serum samples obtained before and after consumption of either EP (500 mg) or placebo were tested in quadruplicates using a double-blinded randomized crossover design. (A) The group averages are shown for changes seen after consumption of placebo versus EP (mean±SD). (B) The individual changes were compared for each subject to evaluate the change in each subject's response to EP in comparison with the same subject's response to placebo. The within-subject paired t test analysis of changes in serum antioxidant protection was calculated. The increased antioxidant protection after EP consumption was statistically significant at 2 hours after consumption (P<.04).

FIG. 7.

Diagram showing proposed mechanisms of action leading to rapid effects on cytokine profile and immune surveillance after consumption of a single acute dose of 500 mg of EP. The rapid increase in serum IFN-γ levels may have contributed to the significant increase in the activation markers CD69 and CD25 on circulating CD3⁻ CD56⁺ NK cells, as well as help to explain the mild but significant transient reduction in circulating T cells and a similar trend for NK cells, indicative of increased immune surveillance.