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2017 Science of Ingredients: Stratum Nutrition (A Business of ESM Technologies, LLC)

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Why is NEM Partially Hydrolyzed?

NEM is a natural joint health ingredient derived from the membrane or inner lining of eggshells. Eggshell membranes, found between the calcified shell and the albumin (egg white) in chicken eggs, are primarily composed of fibrous proteins such as Collagen Type I,1 which form the mesh-like structure of the bi-layered material. However, eggshell membranes have also been shown to contain other bioactive components, namely glycosaminoglycans (i.e. dermatan sulfate,2 chondroitin sulfate,2 hyaluronic acid,3 etc). These bioactive components that are naturally occurring in NEM are also found in joint tissues, namely synovium, cartilage, ligaments and tendons. All of these bioactive components are enmeshed in the macromolecular, sheet-like structure that forms the membrane. In order to free them from the membrane and make them more bioavailable when consumed, NEM undergoes a partial enzymatic digestion as part of the manufacturing process. This initial pre-digestion facilitates the further digestion and ultimate absorption of the important bioactive components of NEM by the human digestive system.

Digestive systems vary widely from person to person. Part of this is due to genetic factors which can lead to differing quantities and types of digestive enzymes produced by each individual. Another part of this is due to environmental factors, such as where a person lives or what type of diet they have that leads to differing levels and species within each individual’s gut microbiota. NEM’s partially hydrolyzed composition ensures that everybody who takes it will be able to digest and absorb enough of the product to feel a benefit. In an inflammation model assay using human immune cells, NEM that had undergone a simulated gastrointestinal digestion was shown to reduce pro-inflammatory cytokines, in particular TNF-α, even more than undigested NEM.4 This direct effect on immune cells is likely attributable to small bioactive polypeptides arising from digestion of protein from NEM.

As people age, their bodies’ ability to tolerate this beneficial microflora can weaken, leading to increased inflammation within the gut which can contribute to a whole host of diseases. Additionally, bacterial cellular components and DNA (thought to have originated in the gut) have been found in the joints of patients suffering from arthritis, and the innate immune response to these contaminants is believed to play a possible role in the development of arthritis in some people. Therefore, immune tolerance is important in preventing arthritis, and NEM was also found to take advantage of the part of the immune system responsible for tolerance.5

Cartilage is primarily composed of extracellular matrix (ECM), a composite network of proteins such as type-II collagen interacting with negatively charged polysaccharides, such as hyaluronic acid and chondroitin sulfate, all of which are synthesized and secreted by the cells of cartilage known as chondrocytes. However, under pathological (disease) conditions, ECM synthesis cannot keep pace with degradation and a loss of the structural integrity of the articular cartilage results. Products of this degradation imbalance can be found in the bloodstream of arthritic patients. The body’s lack of tolerance to these cartilage fragments in the blood is believed to cause the immune system to attack the person’s own cartilage, thereby accelerating the progression of arthritis. The undigested portion of NEM that reaches the intestines contains large fragments of the biopolymers collagen, chondroitin and hyaluronic acid, triggering the immune system to become tolerant to the cartilage fragments of similar composition in the bloodstream. This is why it is important that NEM is only partially hydrolyzed and not fully hydrolyzed.

Partial hydrolysis of NEM allows for two paths to maintain healthy joints. One path occurs through direct modulation of the immune response to joint inflammation via the reduction of pro-inflammatory cytokines. The other path occurs through indirect modulation of the immune response to joint inflammation via oral tolerance. Complete hydrolysis would only allow for the first path to take place and no hydrolysis would only allow for the second path to take place. Partial hydrolysis is key to achieving all of the benefits of both immune modulation pathways.


1 Wong M, et al. Dev Biol. 1984;104(1):28-36.
2 Baker JR, et al. Biochem J. 1962;82:352-361.
3 Long FD, Adams RG, and DeVore DP, Inventors. US Patent #6,946,551. September 20, 2005.
4 Benson KF, et al. J Med Food. 2012;15(4):360-368.
5 Ruff KJ, et al. J Inflamm Res 2015;8:49-57.

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