Ruff K, Morrison D, Duncan S, Back M, Aydogan C, Theodosakis J. Beneficial effects of natural eggshell membrane versus placebo in exercise-induced joint pain, stiffness, and cartilage turnover in healthy, postmenopausal women. Clin Interv Aging. 2018;13:285-295. doi: 10.2147/CIA.S153782
To determine if eggshell membrane (ESM) reduces exercise-induced cartilage turnover, alleviates joint pain, or alleviates joint stiffness.
Randomized, double-blind, placebo-controlled trial
Out of an initial group of 172 postmenopausal women screened, 60 women aged 44 to 74 were enrolled and randomized to either the treatment group (n=30) or the placebo group (n=30). The women included in the study did not have a history of osteoarthritis (OA), rheumatoid arthritis (RA), or other confounding inflammatory joint or connective tissue conditions (eg, gout, lupus), and were restricted from using prescription or over-the-counter (OTC) pain medications, joint supportive supplements, and nonsteroidal antiinflammatory drugs (NSAIDs). All participants were judged, by a medical examination, to be sufficiently healthy to perform moderate exercise.
The treatment group was instructed to take a single 500-mg capsule of Natural Eggshell Membrane (NEM; a brand of ESM) each morning before breakfast; the placebo group consumed a capsule similar in appearance, odor, and taste, on the same schedule.
Exercise consisted of 50 to 100 steps per leg on a 6” aerobic step on alternating days for 2 consecutive weeks. The number of steps was tailored to each patient’s tolerance, determined at screening at the clinical site.
Study Parameters Assessed
Participants were assessed for urinary C-terminal cross-linked telopeptide of type II collagen (uCTX-II) at rest, after 1 week of exercise, and then again after 2 weeks of exercise.
Change in either exercise-induced joint pain or stiffness was evaluated daily via participant questionnaire, with symptoms rated on a 10-point scale. Assessments were performed immediately post-exercise and 12-hours post-exercise, at rest (average from the prior 7 days), and at baseline (immediately following initial exercise screening).
Primary Outcome Measures
The primary endpoint measured for the study was change in exercise-induced cartilage turnover and degradation as assessed via the CTX-II biomarker.
Supplementation with NEM produced a significant treatment response at both 1 week (−17.2%) and 2 weeks (−9.9%) of exercise, compared to placebo. Recovery pain (pain at 12-hours post exercise) was significantly different from placebo from day 8 through day 14, while immediate pain was not significantly different. Both immediate and recovery joint stiffness had significantly different overall trends vs placebo; however, these effects were only seen on certain days throughout the 2-week study period. For the treatment group, both recovery pain and stiffness had nearly returned to resting levels by day 14, and both were significantly lower than the placebo group.
This particular clinical study builds itself from a handful of prior studies that have suggested mechanisms for the chondroprotective effects of ESM. Previous studies have shown a reduction in the cartilage turnover biomarker CTX-II in dogs, while other studies have demonstrated the effects of ESM on nuclear factor (NF)-κB and pro-inflammatory cytokines interleukin (IL)-1β and tumor necrosis factor (TNF)-α, proposing an immunomodulatory mechanism of cartilage protection.1-3 A previous study had also determined that ESM has a beneficial effect on pain and stiffness in knee OA; however, the effects seen in this most recent study seems to be the first piece of evidence suggesting benefits in healthy people.4
Considering the tremendous benefits to be gained from adhering to a consistent exercise program, therapeutic support for the increased stress on joint integrity, and the accompanying discomfort, could be useful in the clinical setting in the immediate and short-term period following exercise resumption.
Despite the statistically significant differences in CTX-II levels vs placebo in the present study, it is difficult to know whether this outcome is clinically relevant. A well-known biomarker for cartilage turnover, CTX-II is associated with the incidence and progression of OA and structural damage in RA; however, it has been highly variable in healthy populations.5-8 The more clinically applicable outcomes from this study are the reduced pain and stiffness.
Exercise is a well-known preventative tool, and a treatment modality for joint and cartilage health and nearly every other condition seen in the clinical setting.9,10 However, with long-term sedentariness, increasing age, and decreased functional capacity, restarting exercise can induce discomfort and pain.9
The beneficial effects of exercise on articular cartilage are well-known, and exercise is essential to maintaining joint health throughout life, yet there is evidence that exercise—either in excessive loads or on weakened joints—can be detrimental to the integrity of articular cartilage.9 These effects can often be silent or accompanied by joint pain, stiffness, or general discomfort in the short term. For individuals who have been sedentary for an extended period of time, these short-term discomforts can be enough of a deterrent to make them stop exercise altogether. Considering the tremendous benefits to be gained from adhering to a consistent exercise program, therapeutic support for the increased stress on joint integrity, and the accompanying discomfort, could be useful in the clinical setting in the immediate and short-term period following exercise resumption.
Considering the limited length of the study (2 weeks), it is difficult to draw conclusions on the effectiveness of NEM over longer periods of time. As discussed above, exercise can cause short-term discomfort and pain, as well as increased articular cartilage turnover when restarting activity following long periods of sedentariness. However, these effects do tend to be self-limiting as cartilage, like other tissues, will adapt to exercise.9
Further, the long-term effects of exercise on articular cartilage, especially in a postmenopausal cohort, are not well understood. The long-term use of NEM has also not yet been investigated, nor have the mechanisms that have been proposed for its beneficial effects on joint pain and stiffness. Considering this, the most useful therapeutic application of NEM seems to be in the short-term resumption of exercise in patients who have been sedentary for an extended period of time. Natural eggshell membrane seems to effectively reduce pain and stiffness in both healthy and OA-afflicted joints, and thus may show benefit for both groups. The decrease in immediate and recovery pain and stiffness during the early phases of restarting exercise may help increase adherence to an exercise plan and reduce relapse back into a state of sedentariness.
If future research is able to further validate a clinically relevant role for addressing CTX-II levels directly, the use of NEM may become more exciting and potentially very useful for treating and preventing degenerative and inflammatory joint conditions.
- Ruff KJ, Kopp KJ, Von Behrens P, Lux M, Mahn M, Back M. Effectiveness of NEM® brand eggshell membrane in the treatment of sub- optimal joint function in dogs: a multicenter, randomized, double-blind, placebo-controlled study. Vet Med (Auckl). 2016;7:113-121.
- Ruff KJ, Durham PL, O’Reilly A, Long FD. Eggshell membrane hydrolyzates activate NF-B in vitro: possible implications for in vivo efficacy. J Inflamm Res. 2015;8:49-57.
- Sakkas LI, Platsoucas CD. The role of T cells in the pathogenesis of osteoarthritis. Arthritis Rheum. 2007;56(2):409-424.
- 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.
- Valdes AM, Meulenbelt I, Chassaing E, et al. Large scale meta-analysis of urinary C-terminal telopeptide, serum cartilage oligomeric protein and matrix metalloprotease degraded type II collagen and their role in prevalence, incidence and progression of osteoarthritis. Osteoarthritis Cartilage. 2014;22(5):683-689.
- van Spil WE, DeGroot J, Lems WF, Oostveen JC, Lafeber FP. Serum and urinary biochemical markers for knee and hip-osteoarthritis: a systematic review applying the consensus BIPED criteria. Osteoarthritis Cartilage. 2010;18(5):605-612.
- Eyre DR, Shao P, Vosberg-Smith K, Weis M, Shaffer K, Yoshihara P. Cross-linked telopeptides from collagen types I, II and III in human urine. J Bone Miner Res. 1996;11(S1):S413.
- Ben Achour W, Bouaziz M, Mechri M, et al. A cross sectional study of bone and cartilage biomarkers: correlation with structural damage in rheumatoid arthritis. Libyan J Med. 2018;13(1):1512330.
- Gahunia H, Pritzker K. Effect of exercise on articular cartilage. Orthop Clin North Am. 2012;43(2):187-199.
- Pisters M, Veenhof C, van Meeteren N, et al. Long-term effectiveness of exercise therapy in patients with osteoarthritis of the hip or knee: a systematic review. Arthritis Rheum. 2007;57(7):1245-1253.