Natural Medicines Comprehensive Database rates effectiveness based on scientific evidence according to the following scale:
The effectiveness ratings for SAMe are as follows:
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Insufficient evidence to rate effectiveness for…
More evidence is needed to rate SAMe for these uses.
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Clinical studies performed as early as 1973 indicated that SAMe had antidepressant effects (38). Over the next two decades, the efficacy and therapeutic benefits of SAMe in depressive disorders was confirmed in over forty clinical trials. Several review articles that summarize these studies were published in 1988 (4), 1989 (5), 1994 (6), and 2000 (12).
In a meta-analysis, conducted by Bressa (6) where twenty-five controlled trials including a total of 791 patients where reviewed. The statistical outcome of this analysis showed that SAMe had a significantly greater response rate than the placebo and was comparable to tricyclic antidepressants. Brown et al (12) summarized the literature on the use of SAMe in depressive disorders up to the time of publication in 2000; they reported that SAMe had been studied in sixteen open, uncontrolled trials (660 patients); thirteen randomized, double-blind, placebo-controlled trials (537 patients); and nineteen controlled trials comparing SAMe with other antidepressants (1134 patients). Significant antidepressant effects were observed in all sixteen open trials. In eighteen controlled trials, SAMe was as effective as was impramine, chlorimipramine, nomifensine, and minaprine. An important observation from these studies is that SAMe had far fewer side effects than other remedies.
The antidepressant effect of SAMe is of particular interest because of the close metabolic relation between folate and SAMe and the association of a high incidence of folate deficiency with depression (39, 40). Experimental animal studies showed that folate deficiency can reduce brain SAMe concentrations (41), and folate-deficient patients were shown to have significantly lower concentrations of SAMe and metabolites of dopamine and serotonin in CSF (42). The restoration of CSF SAMe concentrations after parenteral or oral SAMe dosing, and by inference the replenishment of CNS tissue methyl groups, may in some way be related to the therapeutic effect.
The exact mechanism of the antidepressant effect of SAMe is not clear, although preclinical studies indicated that SAMe has stimulatory effects on monoamine metabolism, monoamine turnover, or both. In agreement with this, SAMe dosing reportedly increased rat brain concentrations of norepinephrine (43, 44) and serotonin (45, 46). In humans, SAMe dosing increased the concentrations of 5-hydroxyindole acetic acid (47), a marker for serotonergic activity. It has been theorized that the stimulatory effect of SAMe on central monoaminergic neurotransmitters is the mechanism underlying its antidepressant effect. Alternative mechanisms may exist in which increased or restored membrane phospholipid methylation plays a role in the antidepressant effect. SAMe, by virtue of its ability to act as a methyl donor, may increase the fluidity of cell membranes by stimulating phospholipid methylation. An increase in cell membrane fluidity was linked to an increase in β receptor density (48) and muscarinic (M1) receptor density (49). The effect of SAMe on receptor systems is of particular interest because evidence suggests that age changes in the membrane environment, especially those resulting in increased viscosity, may be responsible for G protein–receptor coupling-uncoupling dysfunction (50). The therapeutic beneficial effects of SAMe dosing suggest a possible strategy for various systems that exhibit G protein–receptor coupling-uncoupling dysfunction.
In summary, some research suggests that SAMe is more effective than placebo in supporting mild-to-moderate depression without the associated side effects (headaches, sleeplessness, and sexual dysfunction) with other therapeutic alternatives. In addition, other alternatives tend to take 6 – 8 weeks, while SAMe seems to begin more quickly.
Several studies indicate that a Central Nervous System (CNS) methyl group deficiency may play a role in the etiology of Alzheimer disease (AD). Reduced SAMe concentrations were found in Cerebrosipinal Spinal Fluid (CSF) (34) and in several different brain regions (51) of patients with AD. In addition, reduced phosphatidylcholine concentrations were found in postmortem brain tissue from AD patients (52), and significant changes in brain phospholipids that are dependent on SAMe metabolism were detected in vivo with 31p magnetic resonance spectroscopy in the early stages of AD (53). Deficiencies of folate and vitamin B-12 are common in the elderly (39, 40) and can lead to decreased CNS SAMe concentrations. Several studies indicate that elevated blood homocysteine concentrations, considered to be a marker for folate deficiency, vitamin B-12 deficiency, and impaired methylation, may be a risk factor for AD (54–56). It is therefore important to note that preliminary studies using either SAMe (57) or alternative methyl group donors [such as betaine (58) or folate and vitamin B-12 (59, 60)] can support cognitive function. These therapeutic regimens may be able to restore methyl group metabolism and normalize blood homocysteine concentrations. Reduced SAMe concentrations in CSF were also reported in patients with subacute combined degeneration of the spinal cord resulting from folate or vitamin B-12 deficiency (39) and in children with inborn errors of the methyl-transfer pathway who had demyelination (61). In these cases,therapeutic benefits with methyl-group donors such as SAMe, methyltetrahydrofolate, betaine, and methionine was associated with remyelination and a clinical response (61).
In three independent studies, reduced SAMe concentrations in CSF were found in HIV-infected patients; one study was conducted in children (62) and the other two studies were conducted in adults (35, 63). Although the cause of the decreased CSF SAMe concentrations in HIV infection is unknown, it was hypothesized that the resulting methyl-group deficiency may be a pathogenic mechanism involved in the etiology of the vacuolar myelopathy that is often part of the AIDS dementia complex (64). Furthermore, HIV-related vacuolar myelopathy bears a striking histologic resemblance to subacute combined degeneration of the spinal cord, which can accompany folate and vitamin B-12 deficiencies (65). Contrary to the studies discussed above, Goggins et al (66) reported that the amount of radiolabelled SAM incorporated into carboxymethyl and N-methylation sites within brain proteins from cortical white matter in vitro was significantly lower in samples from nine HIV-positive patients than in samples from sixteen control subjects; only four of the nine patients had HIV encephalitis. These data suggest that cortical brain proteins are hypermethylated in HIV-positive patients.
A number of well-designed clinical trials show that SAMe may support pain and inflammation alleviation in the joints, and researchers think it may also assist in cartilage repair, although they are not clear about how or why this works. In several short term studies (ranging 4 – 12 weeks), SAMe supplements were therapeutically effective in adults with knee, hip, or spine osteoarthritis. SAMe was as effectives in diminishing morning stiffness, decreasing pain, reducing swelling, improving range of motion, and increasing walking pace. Several studies also suggest that SAMe has fewer side effects.
The potential therapeutic benefit of SAMe for osteoarthritis was discovered when patients enrolled in clinical trials of SAMe for depression. Participants reported marked improvement in their osteoarthritis symptoms (76). Nine clinical trials in Europe (77) and one in the United States (7) with a total of > 22 000 participants have confirmed the therapeutic activity of SAMe against osteoarthritis.
Experimental studies indicate that SAMe increases chondrocyte proteoglycan synthesis (78) and proliferation rate (79). SAMe induces the synthesis of polyamines which might stabilize the polyanionic macromolecules of proteoglycans and assists attack by proteolytic and glycotic enzymes (80). Furthermore, in vitro studies show that SAMe can antagonize the tumor necrosis factor α–induced decreases in synovial cell proliferation and fibronectin mRNA expression (81). These findings indicate that in cultured synovial cells, SAMe restores basal conditions after cytokine-induced cell damage. In addition, oral administration of SAMe (400 mg for 7 d) to four subjects significantly increased SAMe concentrations in synovial fluid by 3–4-fold compared with pre-dosing values (32).
Fibromyalgia is a chronic condition characterized by pain in the muscles, ligaments, and tendons; fatigue; and multiple tender points on the body. While no one knows what causes fibromyalgia, there is evidence that people with the condition may be more sensitive to pain because something is wrong with the body’s usual pain perception processes. More women than men have fibromyalgia. Fibromyalgia tends to come and go throughout life. It also tends to coexist with sleep disorders, anxiety, depression, and irritable bowel syndrome. Fibromyalgia can be debilitating for some people, but it is not degenerative or life-threatening. You can manage your symptoms and improve your quality of life with professional care and self-care.
No one knows what causes fibromyalgia. Several theories and multiple factors may bring on the condition, including:
Having another rheumatic disease — You may be more likely to get fibromyalgia if you have a disease such as rheumatoid arthritis or lupus.
These nutritional tips may help reduce symptoms:
You can address nutritional deficiencies with the following supplements:
People with liver defects often cannot synthesize SAMe in their bodies, and some preliminary studies suggest that taking SAMe may have some therapeutic benefits for chronic liver disorder caused by medications or alcoholism. A study of 123 men and women with alcoholic liver cirrhosis (liver failure) found that those who consumes SAMe for 2 years improved liver health and delayed the need for liver transplants better than placebo. Other studies show that SAMe may support normalize levels of liver enzymes in people with liver defects. These studies have been small and of short duration. Larger and longer studies are needed to confirm these findings.
The potential therapeutic benefit of SAMe for liver disease stems from several important aspects of SAMe metabolism. In mammals, as much as 80% of the methionine in the liver is converted into SAMe (23). Hepatic glutathione, which is dependent on methionine and SAMe metabolism, is one of the principal antioxidants involved in hepatic detoxification. Studies have shown that abnormal SAMe synthesis is associated with chronic liver disease, regardless of its etiology. Early studies indicated that patients with liver disease are unable to metabolize methionine, resulting in elevated blood concentrations (67). Subsequent studies in patients with liver disease showed that the defect resulted from decreased activity of a liver-specific isoenzyme, MAT I/III; this defect effectively blocks the conversion of methionine to SAMe (68). Several well-designed experimental studies indicated that MAT I/III is regulated by cellular concentrations of both nitric oxide and glutathione. Thus, increased nitric oxide concentrations and decreased glutathione concentrations were shown to inhibit MAT I/III via mechanisms involving increased S-nitrosylation and free radical damage to the enzyme protein (69, 70). Experimental studies and clinical trials showed that parenteral and oral SAMe administration can increase glutathione concentrations in red blood cells (71) and in hepatic tissue (72, 73) and can effectively replenish depleted glutathione pools in patients with liver disease. The literature on the clinical potential of therapeutic benefits of SAMe in the for liver conditions (including cholestasis, hepatitis, and cirrhosis) has been the subject of several review articles (9–11, 74, 75).