When it comes to nutraceuticals that promote joint health, the sky is the metaphorical limit. Choosing the “correct” nutraceutical for a given joint health customer is really a function of the criteria you set up as parameters. For example, if you only want to consider those nutraceuticals with human clinical research to validate their efficacy, that narrows the field somewhat. Now, if you only want to consider those with multiple human clinical studies, that narrows the field considerably more—but there are still several good ones from which to choose. If, however, your selection criteria also include only those nutraceuticals that have also been shown to work in healthy exercising and osteoarthritic populations, your choices are limited to a select few nutraceuticals. Finally, if you want the nutraceutical to provide significant results in just a few days, the pickings are indeed slim. Nevertheless, research suggests that there is still an excellent option that meets all these criteria: natural eggshell membrane (NEM).
NEM is the thin membrane just under the shell that you sometimes have difficulty removing when you’re peeling a hard-boiled egg. NEM is a sustainable food-sourced ingredient composed of fibrous proteins such as collagen types I, V and X, as well as other bioactive components such as glycosaminoglycans (i.e., dermatan sulfate, chondroitin sulfate, and hyaluronic acid)1 and sulfated glycoproteins, including hexosamines such as glucosamine.2 This combination of bioactive components may contribute toward NEM’s multiple mechanisms of action, which may include oral tolerance, suppression of tumor necrosis factor-alpha (TNF-α), and suppression of collagen type II C-telopeptide (CTX-II).
Mechanisms of Action
Oral tolerance refers to the phenomenon of reducing a certain type of immune response (tolerance) that results from the repeated exposure to ingested protein antigens that would otherwise cause a reaction. In-vitro research indicates that, in the case of NEM, this seems to occur via modulation of a transcription factor called NF-κB. Oral tolerance therapy has been shown to be effective in a variety of autoimmune diseases, including arthritis, diabetes, colitis and multiple sclerosis.1
Further research on NEM’s mechanism of action shows its ability to suppress TNF-α, a cell-signaling protein that plays a significant role in the inflammatory process.2 In-vitro research has shown that, by suppressing TNF-α, NEM elicits an anti-inflammatory effect.
CTX-II is a biomarker of cartilage turnover. In human3, dog4 and rat5 studies, NEM has been shown to reduce CTX-II. This suggests that NEM helps reduce cartilage damage. Individually or collectively, these mechanisms of action have demonstrated meaningful joint benefits in healthy and osteoarthritic populations.
Human Clinical Research in a Healthy, Exercising Population
A just-completed two-week, randomized, double-blind, placebo-controlled clinical trial6 evaluated if 500 mg/day NEM (NEM, Stratum Nutrition) would reduce cartilage turnover, as well as reduce joint pain or stiffness, both directly following exercise and 12 hours post-exercise, versus placebo in 60 healthy, post-menopausal women, while performing an exercise regimen on alternating days. Results showed that supplementation with NEM significantly reduced CTX-II versus placebo after both one week and two weeks of exercise. In addition, NEM showed a significant reduction in joint stiffness versus placebo within four days. Likewise, rapid treatment responses were observed at day 14 for recovery pain and stiffness, compared to placebo. The treatment was well tolerated by study participants.
A four-week randomized controlled trial7 was conducted to evaluate the effects of 500 mg/day of Stratum Nutrition’s NEM or placebo on chronic joint pain in 60 physically active adults. Participants also completed a weekly exercise protocol designed to challenge their irritated joint, and then rated their joint pain. Based upon VAS scores, results showed that participants in the NEM group reported significantly less joint pain post-exercise following supplementation when compared to those in the placebo group (p=0.0171). Researchers concluded that NEM supplementation appeared to decrease post-exercise joint pain vs. placebo.
Human Clinical Research in an Osteoarthritic Population
A 60-day, randomized, multicenter, double-blind, placebo-controlled clinical study8 was conducted to evaluate the efficacy and safety of 500 mg/day NEM (Stratum Nutrition) as a treatment for pain and stiffness associated with osteoarthritis of the knee in 67 patients. WOMAC Osteoarthritis Index as well as pain, stiffness, and function WOMAC subscales were used to measure efficacy at 10, 30 and 60 days. Results showed that supplementation with NEM resulted in statistically significant improvements (up to 26.6 percent), versus placebo, at all time points for both pain and stiffness, based upon WOMAC pain and stiffness subscales. Rapid responses were seen for mean pain sub-scores (15.9 percent reduction, P = 0.036) and mean stiffness sub-scores (12.8 percent reduction, P = 0.024) occurring after only 10 days of supplementation. Researchers concluded that supplementation with NEM, 500 mg taken once daily, significantly reduced both joint pain and stiffness compared to placebo at 10, 30 and 60 days.
Two open-label human clinical studies9 were conducted to evaluate the efficacy and safety of 500 mg/day NEM brand as a treatment for pain and inflexibility associated with joint and connective tissue disorders. In the smaller study (which consisted of one group of 11 patients), results were that supplementation with NEM significantly improved flexibility at seven days, (27.8 percent increase; P = 0.038), general pain at 30 days (72.5 percent reduction; P = 0.007), and flexibility (43.7 percent increase; P = 0.006) and range of motion-associated pain at 30 days (75.9 percent reduction; P = 0.021). In the larger study (which consisted of two group of 28 total patients), NEM produced a significant improvement in pain at seven days for both groups (18.4 percent reduction, P = 0.021; and 31.3 percent reduction, P = 0.014). The significant treatment response continued through 30 days for pain (30.2 percent reduction; P = 0.0001), and NEM was well tolerated.
A 60-day, open label, German clinical study10 was conducted to evaluate the efficacy and safety of 500 mg/day NEM brand as a treatment for pain and inflexibility associated with moderate osteoarthritis of the knee and/or hip in 44 patients. Measurements were taken at 10, 30 and 60 days utilizing a 10-question abbreviated questionnaire based on the WOMAC osteoarthritis questionnaire. Results showed that supplementation with NEM produced a significant improvement at 10 days (8.6 percent to 18.1 percent) and at 30 and 60 days (22.4 percent to 35.6 percent improvement) for all nine pain-related questions evaluated. In addition, stiffness improved at 30 and 60 days (27.4 percent to 29.3 percent). More than 59 percent of patients rated the efficacy of NEM as good or very good following 60 days of supplementation. Treatment was well tolerated, and researchers concluded that NEM significantly reduced pain, both rapidly (10 days) and continuously (60 days) demonstrating its safety and efficacy as a therapeutic option for the treating knee and/or hip osteoarthritis pain.
Independently from the German study, a four-week, open-label, Italian clinical study11 was also conducted to evaluate the efficacy and safety of 500 mg/day NEM (Stratum Nutrition) in 25 subjects with moderate osteoarthritis of the knee. Measurements were taken at 10 and 30 days, also using a 10-question abbreviated WOMAC osteoarthritis questionnaire. Supplementation with NEM resulted in reduction in pain at 10 days (40.6 percent p < 0.001) and 30 days (66.4 percent, p < 0.001). There was also a statistically significant reduction in analgesic use during the 30-day study period. Additionally, there was a significant treatment reduction in stiffness at 10 days (22.2 percent, p = 0.009) and 30 days, 59.7 percent, p <0.001). As with the other studies, the treatment was well tolerated. Researchers concluded that NEM is an effective and safe, natural therapeutic option for the treatment of both pain and stiffness associated with osteoarthritis of the knee, with results in 10 days and continued improvement through 30 days, while reducing analgesic intake.
Human clinical research, including randomized controlled trials, have demonstrated the effectiveness of NEM in reducing joint pain and stiffness within four to 10 days, with continuing results over 30-60 days. Furthermore, NEM studies have demonstrated safety and efficacy in healthy exercising populations, as well as in osteoarthritis populations.
1 Ruff KJ, Durham PL, O’Reilly A, Long FD. Eggshell membrane hydrolyzates activate NF-κB in vitro: possible implications for in vivo efficacy. Inflamm Res. 2015 Feb 9;8:49-57.
2 Benson KF, Ruff KJ, Jensen GS. Effects of natural eggshell membrane (NEM) on cytokine production in cultures of peripheral blood mononuclear cells: increased suppression of tumor necrosis factor-α levels after in vitro digestion. J Med Food. 2012 Apr;15(4):360-8.
3 Ruff KJ, Morrison D, Duncan SA, Back M, Aydogan C, Theodosakis J. Beneficial Effects of NEM Brand Eggshell Membrane Versus Placebo in Exercise-induced Joint Pain, Stiffness, & Cartilage Turnover in Healthy, Post-menopausal Women: A Single Center, Randomized, Double Blind, Placebo Controlled Clinical Trial. Unpublished (submitted for publication). 2017:21 pgs.
4 Ruff KJ, Kopp KJ, Von Behrens P, Lux M, Mahn M, Back M. Effectiveness of NEM brand eggshell membrane in the treatment of suboptimal joint function in dogs: a multicenter, randomized, double-blind, placebo-controlled study. Veterinary Medicine: Research and Reports. 18 August 2016;2016(7):113—121.
5 Wedekind KJ, Ruff KJ, Atwell CA, Evans JL, Bendele AM. Beneficial effects of natural eggshell membrane (NEM) on multiple indices of arthritis in collagen-induced arthritic rats. Mod Rheumatol. 2016 Dec 21:1-11.
6 Ruff KJ, Morrison D, Duncan SA, Back M, Aydogan C, Theodosakis J. Beneficial Effects of NEM Brand Eggshell Membrane Versus Placebo in Exercise-induced Joint Pain, Stiffness, & Cartilage Turnover in Healthy, Post-menopausal Women: A Single Center, Randomized, Double Blind, Placebo Controlled Clinical Trial. Unpublished (submitted for publication). 2017:21 pgs.
7 Berardi JM. Can eggshell membrane reduce joint pain? Precision Nutrition. 2012: 1-13.
8 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 Aug;28(8):907-14.
9 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;4:235-40.
10 Danesch U, Seybold M, Rittinghausen R, Treibel W, Bitterlich N. NEM Brand Eggshell Membrane Effective in the Treatment of Pain Associated with Knee and Hip Osteoarthritis Results from a Six Center, Open Label German Clinical Study. J Arthritis. 2014;3:136.
11 Brunello E, Masini A. NEM Brand Eggshell Membrane Effective in the Treatment of Pain and Stiffness Associated with Osteoarthritis of the Knee in an Italian Study Population. Int J Clin Med. 2016;7:169-75.
Gene Bruno, MS, MHS, the dean of academics for Huntington College of Health Sciences, is a nutritionist, herbalist, writer and educator. For more than 30 years he has educated and trained natural product retailers and health care professionals, has researched and formulated natural products for dozens of dietary supplement companies, and has written articles on nutrition, herbal medicine, nutraceuticals and integrative health issues for trade, consumer magazines and peer-reviewed publications. He can be reached at email@example.com.