ABSTRACT
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.