Additional Insights to Mechanism of Action for NEM® Published

MRI-Feb-CoverESM Technologies, the manufacturer of leading eggshell membrane ingredient, NEM® has additional research published to explain how NEM® brand eggshell membrane supports healthy  joints.

NEM® brand eggshell membrane has been shown previously to reduce pro-inflammatory cytokines in-vitro in mitogen-challenged, healthy human immune cells — and now this mechanism of action has been extended to in-vivo studies as well.  The results from these studies, recently published in Modern Research in Inflammation, showed substantial reductions of a variety of pro-inflammatory cytokines while, importantly, having little effect on the anti-inflammatory cytokines evaluated.  The initial studies in healthy rats demonstrated large reductions (up to 88%) in cytokines that occur later in the inflammatory cascade (e.g. MCP-1, MIP-1β, RANTES, VEGF).  Whereas a follow-up study in inflammatory-challenged rats demonstrated significant reductions (40-44%) in IL-1β, a key primary mediator of inflammation.

Kevin J. Ruff, Ph.D., MBA, CCRP – Director of Scientific & Regulatory Affairs for ESM Technologies stated, “We were pleased to find evidence that NEM® helps to maintain a normal inflammatory response in healthy animals.  And the novel nature of this finding formed the basis for a patent (U.S. 8,580,315) that was recently granted for this same indication.”  Taken together, these studies establish that oral supplementation with NEM® can influence quite a number of cytokines associated with the progression of cartilage destruction within joints, providing a plausible basis for the mechanism of action of NEM® in-vivo; and this serves as an important step in explaining its observed clinical efficacy seen in multiple human studies.

These additional published studies show further substantiation for NEM® supporting a healthy inflammatory response.  The paper has published online Modern Research in Inflammation with available open access at


NEM® brand eggshell membrane is a novel dietary supplement that has been clinically shown to alleviate arthritis joint pain and stiffness; however the mechanism of action is not well understood. Preliminary evidence from an in vitro study of NEM® indicated that the mechanism of action may be based on the reduction of pro-inflammatory cytokines. In vivo studies were therefore initiated to evaluate the effects of NEM® on pro-inflammatory and anti-inflammatory cytokines following oral administration in rats. NEM® was administered daily at doses of 6.13 mg/kg bw/day (Study 1), 10.0 mg/kg bw/day (Study 2), or at doses of 0 (control), 26.0 or 52.0 mg/kg bw/day (Study 3) by oral gavage for 7 consecutive days. Inflammation was induced in the Study 3 rats by intraperitoneal injection of lipopolysaccharide. Changes in plasma cytokine levels from baseline following 7 days of oral supplementation with NEM® at 6.13 mg/kg bw/ day (Study 1) were statistically significant at Day 8 for IL-2, TIMP-1 and VEGF, at Day 21 for IL-10, and at Day 35 for MCP-1, MCP-3 and TIMP-1, and at 10.0 mg/kg bw/day (Study 2) were statistically significant at Day 8 for VEGF, at Day 21 for MIP-1β, MIP-2 and VEGF, and at Day 35 for MCP-3, MIP-1β, MIP-2 and VEGF. Changes in serum cytokine levels versus control at 26.0 mg/kg bw/day (Study 3) were statistically significant at all time-points for IL-1β and at 1.5 hours for IL-10, and at 52.0 mg/kg bw/day (Study 3) were statistically significant at 1.5 hours for IFN-γ, IL-1β and IL-10, and at 3 hours for IL-1β, and at 24 hours for IL-10. Taken together, these studies demonstrate that oral supplementation with NEM® can influence both early-phase pro-inflammatory cytokines like IL-1β and TNF-α (Study 3), as well as later-phase cytokines like MCP-1, MIP-1α & β, RANTES and VEGF (Study 1 & 2). These studies provide a possible basis for the mechanism of action of NEM® in vivo.

*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease.
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