Methionine supplement (SAMe) equivalent to celecoxib in OA

[Guest guest]

Rheumawire

Apr 21, 2004

Methionine supplement equivalent to celecoxib in OA

Orange, CA - A popular dietary supplement consisting of

S-adenosylmethionine (SAMe) was found to be as effective as celecoxib

(Celebrex®, Pfizer) in the management of symptoms of knee osteoarthritis

(OA) in a study that followed 56 patients for 16 weeks.

Although it had a slower onset of action, with significantly less pain

relief than celecoxib in the first month of treatment, by the second

month the 2 compounds were " clinically equivalent, " say the researchers,

Dr Wadie Najm and colleagues (University of California, Irvine). The

study is published online in BMC Musculoskeletal Disorders [1].

The supplement is " helpful for the management of pain in osteoarthritis

and demonstrates similar effectiveness as a currently accepted COX-2

inhibitor, " they conclude.

First discovered in Italy in 1952, SAMe has been used in Europe for some

time, often as a prescription product, but it has also become a popular

dietary supplement in the US. SAMe is reported to be effective in the

management of depression, liver disease, and arthritis. In 2002, the US

Agency for Healthcare Research and Quality (part of the Department of

Health and Human Services) reviewed the evidence for these claims. For

osteoarthritis, on the basis of 13 clinical trials, it concluded that

SAMe was better than placebo and not different from nonsteroidal

anti-inflammatory drugs (NSAIDs) at relieving pain [2].

" SAMe is an important physiologic compound that is distributed

throughout the body tissues and fluids, " Najm et al comment. It acts as

a methyl group donor and plays an essential role in many biochemical

reactions involving enzymatic transmethylation, eg, in the biosynthesis

of phospholipids essential for the integrity of cell membranes.

Nevertheless, despite this understanding of its role in the body, its

mechanism of action in disease is unclear, the authors comment. In OA,

there is evidence that it may play a role in reducing inflammation,

increasing proteoglycan synthesis, or by having an analgesic effect,

they add.

Although it is now used orally, SAMe was in the past administered

intravenously because of stability problems, which do not appear to have

been altogether solved. For instance, in this current trial, when about

75% completed, a routine quality check of a random sample of the study

medications indicated that SAMe had lost approximately 51% of its

potency, and the study was delayed until a new batch of SAMe could be

obtained.

The study participants were randomly assigned to 1 of 2 sequences,

receiving either SAMe 600 mg bid for 8 weeks, followed by a 1-week

washout period, and then celecoxib 100 mg bid for 8 weeks, or the other

way around.

Pain was assessed on 2 visual analog scales: patients were asked to rate

the pain they felt that day and also the pain they had felt over the

past month.

After 1 month, celecoxib showed significantly more reduction in pain

than SAMe (p=0.024), but after the second month of treatment, there was

no significant difference between the 2 medications (p<0.01), and both

groups were significantly improved from baseline.

The patients who initially took celecoxib and then the supplement were

" noticeably but not significantly worse " than the group that shifted

from the supplement to celecoxib after the first month of treatment, the

authors note, but there were no apparent differences at the end of the

second month.

Both compounds showed a notable improvement from baseline on most

functional health measures (including overall health, physical fitness,

emotional well-being), with no significant differences between the 2.

Isometric joint-function tests appeared to be steadily improving over

the entire study period regardless of treatment, the authors write. Both

groups showed significant improvements in tenderness in the knee,

swelling in the knee, pain during walking, and in pain frequency.

The most common adverse effects were gastrointestinal disorders

(reported by 4 patients taking SAMe and 6 taking celecoxib), anxiety (5

vs 4), and dyspepsia (1 vs 3); none of these differences was

significant. One patient terminated the study due to headache 3 days

into the SAMe phase, but this patient had a well-known history of such

headaches before enrolling in the study, the researchers comment.

" Our results indicate that SAMe is equivalent in almost all measures to

COX-2 inhibitors (celecoxib) in relieving pain and improving function in

subjects with osteoarthritis of the knee, " Najm et al conclude.

" It is clear from our results that SAMe has a slower onset of action,

requiring almost 1 month of treatment prior to achieving similar effect

to celecoxib, " the researchers continue. In this, the COX-2 inhibitors

and other NSAIDs have " a definite advantage during the first month of

treatment, " they comment.

However, after the second month of treatment, the pain-relieving effect

was equivalent for both drugs, and it is interesting to note that, while

the pain relief of celecoxib was constant throughout the study, the

effect of SAMe continued to increase with time, the authors comment.

" This raises the question of whether the effect of SAMe would have

continued to improve had the study been for a longer period of time. "

Also, the data suggest that the pain relief with SAMe persisted even

after the medication was discontinued, they observe. " In this study, we

noted that subjects who changed from SAMe to celecoxib had an initial

decline in their pain level. " This initial dip beyond the baseline pain

relief obtained by celecoxib alone, while not significant, hints at a

possible persistent effect of SAMe for 1 month beyond discontinuation of

the medication, they say.

" This is reminiscent of reports on the pain-relieving effect observed

with glucosamine sulfate, " they comment. If this result could be

reproduced in future large studies, it may be possible to use SAMe as a

pulsed therapy for the management of pain in OA, after an initial period

to establish a steady level.

Further studies are needed, as there are many questions left unanswered

about this supplement, Najm et al conclude. As well as establishing

optimal dose and mechanism of action, it would be worth exploring

whether the combination of SAMe with a COX-2 inhibitor is more effective

than either alone in the management of osteoarthritis.

Zosia Chustecka

Sources

1. Najm WI, Reinsch S, Hoehler F, et al. S-adenosyl methionine (SAMe)

versus celecoxib for the treatment of osteoarthritis symptoms: a

double-blind cross-over trial. BMC Musculoskelet Disord 2004. Available

at: http://www.biomedcentral.com/1471-2474/5/6.

2. Evidence Report/Technology Assessment: Number 64.

S-Adenosylmethionine for treatment of depression, osteoarthritis and

liver disease. Agency for Healthcare Research and Quality [AHRQ

Publication No. 02-E033]. August 2002. Available at:

http://www.ahrq.gov/clinic/epcsums/samesum.htm.

I'll tell you where to go!

Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

http://www.hopkinsmedicine.org