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NEM, or Natural Eggshell Membrane has popped up as a popular supplement for osteoarthritis sufferers. The companies selling it boast claims about and in ! The pills aren鈥檛 especially expensive, costing only about a day, but the question is whether or not they work.

NEM is said to act as a source of collagen, glucosamine, chondroitin, hyaluronic acid, and calcium, all of which have been investigated extensively for osteoarthritis treatment.

Collagen is the much-hyped novel treatment for everything from arthritis to wrinkles, but . While it plays a very important role as a component of joints, cartilage and ligaments, oral collagen supplements are not likely to mitigate joint pain. There have been several studies done on that show positive results, as well as some on , but there is a lack of relevant . and chondroitin have been thoroughly studied and have been found to lack efficacy in the vast majority of osteoarthritis patients. As far as hyaluronic acid goes, taking oral supplements is .

Calcium supplementation is recommended for patients with (if they aren鈥檛 getting enough dietary calcium), but patients with this condition are , rendering calcium supplementation moot.

So, the individual constituents of NEM don鈥檛 help much, if at all. But what about a combination of these elements?

We have previously addressed Joint Ease Plus, a supplement marketed for arthritis that contains many of the same constituents as NEM. The studies used to support the claims of this supplement were unpublished and聽sketchy to say the least.

At least NEM has current, properly conducted studies on its efficacy. So, what do they say?

Testing any supplement for benefits usually begins with looking for effects in rats or mice. Unlike with human subjects, keeping the rats blinded to what substance they鈥檙e receiving isn鈥檛 relevant, but other tenets of a successful study, like large sample sizes, still apply.

In scientific studies we want to rule out the possibility that results may have occurred due to random chance and we look for 鈥渟tatistical significance鈥� meaning that the results seen were due to whatever intervention was carried out.

Here are some studies that have been carried out in a reasonable fashion.

showed a reduction of some inflammatory cytokines when NEM was given in doses of 6.13-52 mg/kg of body weight (equivalent to 59-503 mg per day in a 60 kg person), but their sample size was low, only 3 rats for the lower doses and 8 for the higher. found similar results, but only used 7 rats.

looked at NEM in conjunction with goat fat as a source of omega-3 fatty acids in a range of doses, and found positive results based on knee diameter (a marker of swelling) and animal behaviour, albeit using sample sizes of 5 per dose.

used a sample size of 54, and found similarly positive results in reduction of ankle diameter, lower ankle and knee histopathology scores and lowered the amount of pro-inflammatory cytokines found in the blood.

However, it鈥檚 hard to say whether a supplement giving statistically significant results in rats will give statistically significant results in humans (their biology is similar but not the same). Furthermore, it鈥檚 even harder to say whether those results in humans will be clinically significant. You could have a reduction in pain that, while statistically significant, is too miniscule to matter to a patient. That鈥檚 why testing on humans is the important criterion.

So, onwards to the human studies.

involved 37 patients and gave them 500 mg of NEM daily for 8 weeks. Based on questionnaires in which patients rated their pain on a scale of 1-10, statistically significant results ranging from 22.4% to 35.6% improvement were seen. That means that with the best results patients went from rating their pain on average a 3.4 to a 2.2 out of 10. It鈥檚 not nothing, but it鈥檚 not a miracle cure either.

But (there鈥檚 always a but), this study lacked the very important placebo control. Without that it鈥檚 impossible to say whether NEM works any better than a sugar pill, and this is especially important since glucosamine just barely works better than a placebo.

was placebo controlled, and double blind. It involved 25 patients, 13 of which were treated with 450 mg per day of 庐 (made from water soluble egg membrane), the other 12 with a placebo. Sadly, the study doesn鈥檛 actually tell us what is in BiovaFlex庐. Their website mentions collagen, elastin and a few other ingredients, but still doesn鈥檛 give amounts. So, even though the study showed pretty good results, like a 45% pain reduction in upper back pain at rest with BiovaFlex庐 vs. 23% reduction for placebo, we can鈥檛 really derive anything from this study except that BiovaFlex庐 works decently. Of course, the company also sponsored the study, so take these results with a grain of salt.

was also placebo controlled, and double blind, with 31 subjects receiving placebo and 29 subjects receiving 500 mg NEM daily. However, there was a roughly 40% dropout rate. That doesn鈥檛 discount the trial, but it doesn鈥檛 bode well, considering 9 patients receiving NEM dropped out due to a lack of efficacy. Still, with those remaining subjects, the study found statistically significant results for reductions in pain and stiffness at 30 and 60 days post treatment, but insignificant results for an improvement of function or overall joint health.

Another study found that NEM when given in 500 mg doses to healthy postmenopausal women who experiences low levels of pain (less than or equal to a 3/10), but that鈥檚 hardly the target audience for joint pain reduction.

Perhaps the most interesting of the studies, examined the efficacy of NEM in general, as well as the degree to which hydrolysis of eggshell membrane prior to blending into supplement form may affect its effects. It first used 11 patients to test 500 mg of daily NEM and found reductions in overall pain relevant only after 30 days, but an increase in flexion significant after 7. The most striking result was a 75.9% improvement in range-of-motion related pain after 30 days. The researchers then compared a 2.5 x more hydrolyzed version of NEM with the normal version and found (using 14 subjects) that the more hydrolyzed version doubled the percent improvement of patients (18.4% vs 31.3%). These results seem to hugely support NEM as a supplement, specifically a more hydrolyzed version of it (they never discuss what effect the increased hydrolysis has on the supplement, but it likely breaks proteins down further and facilitates their absorption). However, this study wasn鈥檛 blinded, wasn鈥檛 placebo controlled, and most importantly the patients tested didn鈥檛 have arthritis. Those recruited only needed to rate their pain as 2/10 to qualify as subjects.

These results are all pretty lackluster and point to NEM helping only minimally with pain and stiffness, both in those with and without arthritis. Arthritis supplement studies in general show us how statistical significance and clinical significance are not the same thing.

On a positive note however, NEM is safe. No study found adverse effects as exemplified by on its safety which found no toxicity at doses up to 2000 mg/kg body weight per day in rats.

Bottom line: The evidence for Natural Eggshell Membrane helping with arthritis is pretty thin.

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