Pre-Clinical Study on NEM® Published in the Journal of Medicinal Food

A new pre-clinical research study on NEM®, published in the Journal of Medicinal Food April 2012, looks at NEM’s mechanism of action in order to gain insight into NEM’s clinical efficacy in reducing joint pain and stiffness. It has been published online ahead of print, (

When human immune cells were exposed to a water extract of NEM® and subsequently compounds that are known to cause an inflammatory response, NEM® was shown to significantly reduce a number of pro-inflammatory cytokines. This effect was most pronounced for the cytokines Interferon-gamma (IFN-g) and Tumor Necrosis Factor-alpha (TNF-α). The reduction in TNF-α was further enhanced by a simulated gastric digestion, likely giving insight into the compounds produced in the stomach following digestion of NEM®. TNF-α plays an important role in inflammatory processes, particularly chronic joint inflammation. This preliminary work demonstrates that NEM®’s ability to reduce joint pain and stiffness may well be a result of its ability to reduce TNF-α systemically or locally in the joints.

Of special interest is the methodology used in the publication.  The bioactivity of NEM® was compared to a digested sample of the same product/lot.  The digestion mimicked specific phases of the human digestive processes (acid/pepsin, followed by bile enzymes and salts) and was performed using an in vitro digest protocol at NIS Labs (Klamath Falls, OR).

The testing was performed to examine whether the biological properties of NEM® were preserved or enhanced after digestion.  The data showed that specific anti-inflammatory properties were enhanced after the in vitro digest.  Where the crude product suppressed the inflammatory cytokine TNF-alpha production in cultures of human immune cells, the NEM® after an in vitro digest produced similar effect at 100 times lower doses, suggesting stronger anti-inflammatory effects after digestion.


Tumor necrosis factor alpha (TNF-a) plays an important role in inflammatory processes. This study examined the effects of NEM® (Natural Eggshell Membrane) on IL-2, IL-4, IL-6, IL-10, interferon gamma (IFN-g) and TNF-a cytokine production by 4-day peripheral blood mononuclear cell (PBMC) cultures exposed to serial dilutions of either an aqueous extract of natural eggshell membrane (NEM-AQ) or NEM® subjected to in vitro digestion (NEM-IVD).  The effects on cytokine production were also assessed in the presence of phytohemagglutinin (PHA) and Pokeweed mitogen (PWM), where exposure to NEM-AQ resulted in reduced levels of proliferation and statistically significant effects on IL-6, IL-10, IFN-g and TNF-a cytokine production.  NEM-AQ reduced levels of IL-6, IL-10, IFN-g and TNF-a in cultures exposed to PHA.  In cultures containing PWM, NEM-AQ reduced production of IL-10 and at the highest dose tested increased IL-6 and decreased TNF-a cytokine levels.  The in vitro digest of NEM® (NEM-IVD), at the two lowest concentrations of product, significantly reduced TNF-a production  by PBMC cultures exposed to PWM compared to the in vitro digest control or native NEM.  Taken together, these results suggest that NEM-AQ can influence signaling events in response to the T cell-specific mitogen PHA, as well as the mitogen PWM that requires cellular cross-talk and these effects may be partially mediated through a reduction in the pro-inflammatory cytokine TNF-a. The suppression of TNF-a production in the presence of the in vitro digested NEM-IVD is promising for NEM as a consumable anti-inflammatory product.

*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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