Download NEM (Natural Eggshell Membrane)

Natural Eggshell Membrane or NEM
The naturally occurring substances in eggshell membranes that allow them to keep the
cartilage and synovium healthy are glycosaminoglycans and a mixture of proteins such as
collagen, hyaluronic acid, chondroitin sulfate, and glucosamine. So not only do they already
contain two effective cures for arthritis, chondroitin and glucosamine, but it also has proteins
making this a very effective natural cure for the pain and stiffness of arthritis and osteoarthritis.
Many of the various components present in EM have been thoroughly analyzed.
Eggshells consist of a number of layers: an inner and outer membrane, a mammillary layer
(connecting the eggshell and outer membrane), an outer palisade layer, and an outer cuticle
covering the eggshell [1]. The inner and outer shell membranes are the first layers of
extracellular matrix covering the egg itself [2]; the outer membrane is predominantly made of
type I collagen, whereas the inner membrane consists mainly of type V collagen [3]. In addition,
type X collagen has been reported to occur in both of these membrane structures [1]. EM amino
acid profiles have also shown high concentrations of arginine, glutamic acid, histidine, cystine
and proline [4]. Additionally, a number of collagen-like proteins (including hydroxyproline,
hydroxylysine, desmosine, and isodesmosine) are primary structural components of the
membranes. [5,6]
Other components have been quantified in EM including: lysyl oxidase (reported to play
a role in the development and repair of connective tissue), ovotransferrin, and lysozyme [8-11].
However, the presence of glycosaminoglycans in EM is of particular interest.
Glycosaminoglycans (GAGs), such as dermatan sulfate and chondroitin sulfate [7], hexosamines,
such as glucosamine, as well as hexoses and fucose [8] and act as major components of
connective tissue [11-16]. Also significant amounts of hyaluronic acid have been detected in
eggshell membrane[12]
Clearly, there are a number of individual components present in the EM that have known
physiological roles in joint and connective tissue; however, EM is novel in that it is a natural
extract that provides a combined source of these compounds. The absolute quantity of each
component in the EM is not known, and those quantities may likely vary with each extraction in
the supplement production process. Additionally, it is plausible that a number of yet unisolated
elements, proteins, and enzymes exist in EM, which may also contribute to improved joint and
connective tissue health. Therefore, the observed benefits associated with EM supplementation
may not be directly attributable to any one specific component of the supplement (ie.
glucosamine, chondroitin, etc.); it may be more appropriate to assume that the combined effects
of the known—and unknown—components of EM contribute to the observed improvements in
joint health.
A number of individual components in EM are known to have important roles in
maintaining connective tissue in vivo, though the physiological mechanisms by which those
components improve overall joint health through supplementation (flexibility, connective tissue
repair and maintenance) have not been measured in humans. One experiment, however,
investigated the effects of EM supplementation on systemic pro- and anti-inflammatory markers
in rats [17]. In this study, rats were given oral doses of EM for 7 days. Significant decreases were
observed in plasma levels of numerous inflammatory antigens following supplementation; thus,
it is possible that the anti-inflammatory effects of oral EM supplements may contribute to the
improvements in joint pain ratings seen in human trials
Clinical Studies[18,19]
Eggshell membrane: A possible new natural therapeutic for joint and connective
tissue disorders. Results from two open-label human clinical studies
NEM® open label human clinical trials
Clin Interv Aging. 2009; 4: 235–240.
Published online Jun 9, 2009.
PMCID: PMC2697588
Kevin J Ruff,1 Dale P DeVore,2 Michael D Leu,3 and Mark A Robinson4
ESM Technologies’ NEM® brand eggshell membrane is a proven ingredient for the joint health market
that delivers fast results. Two 30-day open label human clinical trials were conducted to evaluate NEM®
(500mg once daily) for supporting joint and connective tissue.
Effect of NEM® on Joint Comfort
The results of the studies showed that supplementation with NEM® produced an average 25%
improvement in joint comfort (both Study 1 & Study 2) in just 7 days. By the end of the 30-day trial,
patients in Study 1 had an average improvement in comfort of more than 72%. Patients in Study 2
experienced more moderate relief with an average 30% improvement in comfort at the completion of
the trial, however about one-third of them experienced more than 50% improvement in comfort. No
side effects were reported by study participants in either trial.
Effect of NEM® on Range of Motion
Supplementation with NEM® also produced an average 28% increase in flexibility in just 7 days for
patients in Study 1. Flexibility had improved by an average 44% by the end of the study with more than
half of the patients experiencing greater than 50% improvement in flexibility by day 30. NEM® not only
improved joint flexibility, it also improved joint comfort in patients while flexing the affected joint in a
range of motion (ROM) evaluation. At day 7, patients had 43% less discomfort while flexing, and by day
30, this had improved to 76% less discomfort while flexing. Again, no side effects were reported by study
participants.
Supplementation with NEM® produced a significant treatment response at:

7 days for flexibility (27.8% increase, P = 0.038)

30 days for general discomfort (72.5% reduction, P = 0.007)

30 days for flexibility (43.7% increase, P = 0.006)

30 days for ROM-associated discomfort (75.9% reduction, P = 0.021)
Another study:
Eggshell membrane in the treatment of pain and stiffness from osteoarthritis of the
knee: a randomized, multicenter, double-blind, placebo-controlled clinical study
Clin Rheumatol. Aug 2009; 28(8): 907–914.
Published online Apr 2, 2009. doi: 10.1007/s10067-009-1173-4
PMCID: PMC2711914
Kevin J. Ruff,
1
Anne Winkler,2 Robert W. Jackson,3 Dale P. DeVore,4 and Barry W. Ritz5
In the double-blind, placebo-controlled Osteoarthritis Pain Treatment Incorporating NEM
clinical study researchers investigated the effects and safety natural eggshell membrane for pain
and stiffness in osteoarthritis of the knee. Sixty-seven study participants took 500 mg of NEM
daily for eight weeks. They were evaluated at 10, 30 and 60 days for joint pain, stiffness and
function using the Western Ontario and McMaster's Universities (WOMAC) osteoarthritis index.
The results were statistically significant. On average, natural eggshell membrane reduced
pain by nearly 16 percent and reduced stiffness by almost 13 percent within just 10 days. In just
10 days, thirty-three percent of the NEM participants experienced more than a 30 percent
reduction in pain and a quarter of them had more than a 50 percent improvement in stiffness.
What's even more impressive if you're seeking a new and improved osteoarthritis
treatment, is that the effects of natural eggshell membrane were not short term. After 60 days, 32
percent of the NEM group had more than a 50 percent reduction in pain. Their stiffness also
continued to get better, with an average 27 percent reduction compared to the placebo group. By
the end of the trial natural eggshell membrane had reduced stiffness by half for the majority of
the patients.
In a press release from ESM Technologies, the company that developed natural eggshell
membrane, Anne Winkler, a rheumatologist and one of the study's authors said: "What I found
most remarkable about the study was the quickness in which people responded to the eggshell
membrane preparation. Generally, we tell patients taking over-the-counter products that contain
glucosamine that it may be two to three months before they notice any benefits. The fact that
within a fairly short period of time they noticed a definite improvement in [their symptoms] was
impressive."
References:
1. Arias JL, Fernandez MS, Dennis JE, Caplan AI: The fabrication and collagenous
substructure of the eggshell membrane in the isthmus of the hen oviduct. Matrix 1991,
11(5):313-320.
2. Creger CR, Phillips H, Scott IJ: Formation of an eggshell. Poultry Sci 1976, 55:17171723.
3. Wong M, Hendrix MJ, von der Mark K, Little C, Stern R: Collagen in the egg shell
membranes of the hen. Dev Biol 1984, 104(1):28-36.
4. Britton WN, Hale KK: Amino acid analysis of shell membranes of young and old hens
varying in shell quality. Poultry Sci 1977, 56:865-871.
5. Baker JR, Balch DA: A study of the organic material of hen's-egg shell. Biochem J 1962,
82:352-361.
6. Candlish JK, Scougall RK: L-5-hydroxylysine as a constituent of the shell membranes of
the hen's egg. Int J Protein Res 1969, 1(4):299-302.
7. Baker JR, Balch DA (1962) A study of the organic material of hen's-egg shell. Biochem J
82:352–361 [PMC free article] [PubMed]
8. Picard J, Paul-Gardais A, Vedel M (1973) Sulfated glycoproteins from egg shell
membranes and hen oviduct. Isolation and characterization of sulfated glycopeptides.
Biochimica et Biophysica Acta 320:427–441 [PubMed]
9. Long FD, Adams RG, and DeVore DP (September 20, 2005) Preparation of hyaluronic
acid from eggshell membrane. USA Patent #6946551
10. Nakano T, Ikawa NI, Ozimek L (2003) Chemical composition of chicken eggshell and
shell membranes. Poult Sci 82:510–514 [PubMed]
11. Starcher BC, King GS: The presence of desmosine and isodesmosine in eggshell
membrane protein. Connect Tissue Res 1980, 8(1):53-55.
12. Akagawa M, Wako Y, Suyama K: Lysyl oxidase coupled with catalase in egg shell
membrane. Biochim Biophys Acta 1999, 1434(1):151-160.
13. Gautron J, Hincke MT, Panheleux M, Garcia-Ruiz JM, Boldicke T, Nys Y:
Ovotransferrin is a matrix protein of the hen eggshell membranes and basal calcified
layer. Connect Tissue Res 2001, 42(4):255-267.
14. Hincke MT, Gautron J, Panheleux M, Garcia-Ruiz J, McKee MD, Nys Y: Identification
and localization of lysozyme as a component of eggshell membranes and eggshell matrix.
Matrix Biol 2000, 19(5):443-453.
15. Kjellen L, Lindahl U: Proteoglycans: structures and interactions. Annu Rev Biochem
1991, 60:443-475.
16. Nakano T, Ikawa N, Ozimek L: Extraction of glycosaminoglycans from chicken eggshell.
Poult Sci 2001, 80(5):681-684.
17. DeVore DP, Long FD, Osborne MP, Adams RG, Franklin MR: Anti-inflammatory
activity of eggshell membrane and processed eggshell membrane preparations. 2007,
10/797,747(US 2007/0178170 A1).
18. Ruff KJ, DeVore DP, Leu MD, Robinson MA: Eggshell membrane: a possible new
natural therapeutic for joint and connective tissue disorders. Results from two open-label
human clinical studies. Clin Interv Aging 2009, 4:235-240.
19. Ruff KJ, Winkler A, Jackson RW, DeVore DP, Ritz BW: Eggshell membrane in the
treatment of pain and stiffness from osteoarthritis of the knee: a randomized, multicenter,
double-blind, placebo-controlled clinical study. Clin Rheumatol 2009, 28(8):907-914.