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Relation
Ruff K, Morrison D, Duncan S, Back M, Aydogan C, Theodosakis J. Beneficial effects of natural eggshell membrane compared to placebo on exercise-induced joint pain, stiffness and cartilage turnover in healthy postmenopausal women.Clin Interv Aging. 2018;13:285-295. (link removed)
Objective
To determine whether the eggshell membrane (ESM) reduces stress-induced cartilage turnover, relieves joint pain, or relieves joint stiffness.
Draft
Randomized, double-blind, placebo-controlled trial
Participant
From an initial group of 172 screened postmenopausal women, 60 women aged 44 to 74 were enrolled and randomly assigned to either the treatment group (n=30) or the placebo group (n=30). Women included in the study had no history of osteoarthritis (OA), rheumatoid arthritis (RA), or other confounding inflammatory joint or connective tissue diseases (e.g., gout, lupus) and were prohibited from using prescription or over-the-counter (OTC) pain relievers, joint-support supplements, and nonsteroidal anti-inflammatory drugs (NSAIDs). All participants were assessed by medical examination as sufficiently healthy to perform moderate exercise.
intervention
The treatment group was instructed to take a single 500 mg Natural Eggshell Membrane (NEM; a brand of ESM) capsule each morning before breakfast; The placebo group took a capsule with a similar appearance, smell and taste on the same schedule.
Training consisted of 50 to 100 steps per leg on a 6-inch aerobic step on alternate days for 2 consecutive weeks. The number of steps was tailored to each patient's tolerance, which was determined at screening in the clinical center.
Study parameters assessed
Participants were examined for C-terminally cross-linked type II collagen telopeptide (uCTX-II) in urine at rest, after 1 week of training, and then again after 2 weeks of training.
Change in exercise-induced joint pain or stiffness was assessed daily via a participant questionnaire, with symptoms rated on a 10-point scale. Assessments were conducted immediately after training and 12 hours after training, at rest (average of the previous 7 days), and at baseline (immediately after the initial training screening).
Primary outcome measures
The primary endpoint measured for the study was change in load-induced cartilage turnover and degradation as assessed by the CTX-II biomarker.
Key insights
NEM supplementation resulted in a significant treatment response compared to placebo at both 1 week (-17.2%) and 2 weeks (-9.9%) of exercise. Recovery pain (pain 12 hours after exercise) was significantly different from placebo from Day 8 to Day 14, while immediate pain was not significantly different. Both immediate and recovery joint stiffness had significantly different overall trends versus placebo; However, these effects were only observed on certain days during the two-week study period. In the treatment group, both recovery pain and stiffness had returned to near resting levels by day 14, and both were significantly lower than in the placebo group.
Practice implications
This particular clinical trial builds on a handful of previous studies that have proposed 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 the proinflammatory cytokines interleukin (IL)-1β and tumor necrosis factor (TNF)-α, suggesting an immunomodulatory mechanism of cartilage protection.1-3A previous study had also found that ESM had a positive effect on pain and stiffness in knee OA; However, the effects observed in this latest study appear to be the first evidence suggesting benefit in healthy people.4
Given the tremendous benefits that come from adhering to a consistent exercise program, therapeutic support for the increased stress on joint integrity and associated discomfort could be useful in the clinical setting in the immediate and short-term period following resumption of exercise.
Despite the statistically significant differences in CTX-II levels versus placebo in the present study, it is difficult to say whether this result is clinically relevant. CTX-II, a well-known biomarker of cartilage turnover, is associated with the occurrence and progression of OA and structural damage in RA; However, it was highly variable in healthy populations.5-8The more clinically applicable results of this study are the reduction in pain and stiffness.
Exercise is a well-known preventive tool and treatment modality for joint and cartilage health and for almost all other conditions encountered in the clinical setting.9.10However, with prolonged lack of exercise, increasing age and reduced functionality, resuming training can lead to discomfort and pain.9
The beneficial effects of exercise on articular cartilage are well known, and exercise is essential for maintaining joint health throughout life. However, there is evidence that exercise – either with excessive stress or with weakened joints – can compromise the integrity of articular cartilage.9These effects can often be silent or accompanied by joint pain, stiffness, or general discomfort in the short term. For those who have been sedentary for an extended period of time, these short-term discomforts can be enough of a deterrent to cause them to stop exercising altogether. Given the tremendous benefits that come from adhering to a consistent exercise program, therapeutic support for the increased stress on joint integrity and associated discomfort could be useful in the clinical setting in the immediate and short-term period following resumption of exercise.
Given the limited study duration (2 weeks), it is difficult to draw conclusions about the effectiveness of NEM over longer periods. As discussed above, exercise can cause short-term discomfort and pain as well as increased articular cartilage turnover when activity is resumed after long periods of sitting. However, these effects tend to be self-limiting because cartilage, like other tissues, adapts to loading.9
Furthermore, the long-term effects of exercise on articular cartilage, particularly in a postmenopausal cohort, are not well understood. Long-term use of NEM has also not yet been studied, nor have the mechanisms proposed for its beneficial effects on joint pain and stiffness. In view of this, the most useful therapeutic application of NEM appears to be in the short-term resumption of exercise in patients who have been sedentary for a long period of time. Natural eggshell membrane appears to be effective in reducing pain and stiffness in both healthy and OA-affected joints and therefore may show benefit for both groups. Decreasing immediate and recovery pain and stiffness during the early stages of resumption of exercise may help improve adherence to an exercise plan and reduce relapse into a sedentary state.
If future research is able to further validate a clinically relevant role for direct treatment of CTX-II levels, the use of NEM may become more exciting and potentially very useful for the treatment and prevention of degenerative and inflammatory joint diseases.