ESTES PARK, COLO. – S-adenosyl-L-methionine (SAMe) doesn’t crack the annual top-10 lists of the most widely used supplements in complementary and alternative medicine surveys. But unlike other more popular products, SAMe is supported by randomized trial evidence of efficacy for osteoarthritis, depression, and fibromyalgia.
Indeed, SAMe is "buzz worthy," Dr. Lisa Corbin declared at an update on internal medicine sponsored by the University of Colorado.
The Natural Medicines Comprehensive Database, which she cited as the best available source of physician information on supplements, rates SAMe as "likely effective" for depression and osteoarthritis and "possibly effective" for fibromyalgia, noted Dr. Corbin, medical director of the University of Colorado Hospital’s Center for Integrative Medicine in Aurora and a general internist at the university.
The Natural Medicines Comprehensive Database is subscription funded and eschews financial support from industry. The organization is famously tough in its efficacy ratings. "Likely effective" is about as good as it gets. Take, for example, hypertension. Nothing included in the natural medicines database has earned the coveted "effective" rating for treatment of hypertension, and only a single item is listed as "likely effective": the National Institutes of Health–backed DASH diet.
SAMe is a naturally occurring homocysteine derivative present in all living human cells. Its synthesis is related to vitamin B12/folate metabolism, and SAMe serves as an essential methyl donor in cellular metabolism.
Depression
The mechanism of SAMe’s antidepressant effect involves boosting norepinephrine and dopamine, as well as increased serotonin turnover. Neuroimaging studies and EEGs show changes in patients on SAMe similar to those seen with conventional antidepressant medications.
An early meta-analysis of many small studies showed that SAMe was superior to placebo, with an efficacy equivalent to that of tricyclic antidepressants, the state-of-the-art antidepressant medications of that era (Acta Neurol. Scand. Suppl. 1994;154:7-14).
More recently, investigators at Massachusetts General Hospital, Boston, conducted a double-blind randomized trial in 73 adults with major depressive disorder, all with an inadequate response to adequately dosed serotonin reuptake inhibitors. They continued on their antidepressant and were randomized to add-on placebo or SAMe at 400 mg b.i.d., increased after 2 weeks to 800 mg b.i.d.
The response rate as defined by a greater than 50% improvement in Hamilton Rating Scale for Depression scores after 6 weeks was 36% in the SAMe group, more than twice the rate in the placebo arm. Remission as defined by a HAM-D score below 7 occurred in 26% of the SAMe group compared with 12% of controls. Both between-group differences were statistically significant.
The investigators calculated the number-needed-to-treat as 6 to obtain one additional clinical response more than with placebo plus a serotonin reuptake inhibitor. The NNT for one additional remission was 7 (Am. J. Psychiatry 2010;167:942-8). "Those are actually pretty good NNTs," the internist observed.
Osteoarthritis
SAMe appears to increase proteoglycans synthesis and has analgesic and anti-inflammatory effects. Numerous small studies of varying quality have demonstrated a benefit similar to non-cyclo-oxygenase 2--selective NSAIDs, but with fewer side effects.
In a University of California, Irvine, 16-week, double-blind, crossover trial involving 61 patients with knee osteoarthritis, SAMe dosed at 400 mg t.i.d and celecoxib at 200 mg/day demonstrated comparable pain reduction and improvement over time in functional health scores and isometric joint function tests.
SAMe was slower acting, taking almost a month to catch up to the COX-2 inhibitor in terms of analgesic effect. On the other hand, it appeared that the benefits of SAMe lasted after the medication was stopped (BMC Musculoskelet. Disord. 2004 [doi:10.1186/1471-2474-5-6]) .
Fibromyalgia
Danish rheumatologists randomized 43 patients with fibromyalgia to 800 mg/day of SAMe or placebo double-blind for 6 weeks. The SAMe group showed significant improvement compared with controls in fatigue, clinical disease activity, pain during the past week, mood, and morning stiffness, but not in tender point score or isokinetic muscle strength. Side effects in the SAMe group were no different than with placebo (Scand. J. Rheumatol. 1991;20:294-302).
Another Danish double-blind randomized trial compared intravenous SAMe – a route of administration almost never used today – to placebo in 34 fibromyalgia patients. Ten days of IV SAMe at 600 mg/day showed nonsignificant trends for better outcomes than with placebo (Scand. J. Rheumatol. 1997;26:206-11).
Dr. Corbin said there have been no major safety issues with SAMe. At higher doses it has been associated with gastrointestinal side effects, headache, and loss of appetite.
"I think the financial toxicity is a potential issue," she quipped.
She said she urges her patients who are interested in trying dietary supplements to seek out those with ‘USP Verified’ displayed prominently on the label. That designation signals that the product meets rigorous United States Pharmacopeia quality standards. However, SAMe is not a big seller, and no USP standards have been set for it. So she recommends that patients scan the shelves and select a SAMe product marketed by a company with USP labels on plenty of their other, more common supplements.