SAMe 400mg - 60 Tabs + BONUS

SAMe from AOR
S-Adenosyl-l-methiononine, or SAMe, is a naturally-occurring physiological agent in the human body that forms an integral part of the methylation cycle. It is formed in the body through the combination of the amino acid methionine and adenosine triphosphate (ATP). This compound was first isolated in Italy in 1952 and is now a recommendation drug in much of Europe, most commonly it seems, as an anti-depressant. Safe, energizing, and purported to treat depression twice as fast as standard anti-depressants such as Prozac^TM, SAMe has become more popular than the latter in the nation of its discovery, in spite of being more expensive there. SAMe is also heavily studied for its ability to alleviate the conditions of osteoarthritis as well as to treat liver disease.

Biochemical Mechanism of Action for the Methylation Cycle
SAMe, which is found in every living cell, begins with the essential amino acid methionine. Methionine then binds with adenosine triphosphate (ATP) to create SAMe. SAMe's creation is immediately followed by the donation of its methyl group (comprised of the 4 atoms at the tail end of the original amino acid methionine) to another molecule called a methyl acceptor. After SAMe has imparted its methyl donor it is converted to SAH, or S-Adenosylhomocysteine, which is rapidly broken down to form homocysteine. This is a potentially dangerous situation as homocysteine is essentially metabolic waste which can be toxic. Fortunately, it only exists as an intermediary product to be broken down by the B-complex vitamins, especially B6, B12, and folic acid. B6 breaks homocysteine down to cysteine, which in turn binds with glutamic acid and glycine to form glutathione. Vitamins B12 and folic acid for their parts convert homocysteine back into methionine, thus ending (and re-starting, or "remethylating") the methylation cycle.

Methylation
Methylation is one of the most common metabolic functions of the body, occurring on the order of a billion times per second. The methylation cycle affects everything from central nervous system activity to cholestasis of pregnancy. As the body ages, the outer lipids of the cells harden, but methylation keeps that layer supple. For this reason, it is theorized that in order to help stymie the process of cellular aging, the body needs a constant and steady supply of methyl donors, of which SAMe is among the most prolific. It must be noted that it is critical to maintain adequate vitamin B supplies as they seem to work synergistically with SAMe for converting homocysteine into its more productive metabolites.

SAMe and Depression
It is as an anti-depressant that SAMe seems to have established itself in the collective mindset of the scientific community. At first glance, this sounds like a scientific stretch when the aforementioned biochemical functions of SAMe are re-examined. However, as was previously noted, the influence of the methylation cycle is so widespread that it affects factors of the central nervous system that are directly pertinent to depression.

To begin with, methionine requires one carbon groups (primarily from glycine and serine) to begin the methylation cycle. These one-carbon groups rely heavily on the B-complex vitamins, especially folic acid and B-12, for their amalgamation by methionine for the methylation cycle and the subsequent conversion to SAMe. The fact that inadequate concentrations of these vitamins are synonymous with depression have led researchers to theorize that supplemental SAMe enhances the metabolism of the B family of vitamins (especially folic acid), thus explaining the anti-depressant power within SAMe's range of benefits.

Monoamine Neurotransmitters
Another possible (and perhaps concurrent) explanation of SAMe's anti-depressant properties is its effect on monoamine neurotransmitters in the brain, especially serotonin and dopamine. Serotonin is formed from tryptophan and has an important effect on learning, sleep, and the regulation of mood. The latter's connection to depression is quite palpable, and SAMe is widely known to raise serotonin levels in the brain, providing another possibly accumulative avenue for the speed and effectiveness of its anti-depressant activity. Dopamine is another monoamine neurotransmitter that likely plays an even bigger role in the averting of depression than serotonin. Dopamine is formed in the brain by the decarboxylation of L-dopa, and lower concentrations of dopamine are not only affiliated with the conditions of depression (as are lower concentrations of serotonin) but they are also closely associated with Parkinson's disease as well. SAMe's effect on depression may also be linked to the hormone melatonin. Produced by the pineal gland, melatonin is derived from serotonin and plays an important role in sleep and by extension the aging process. Like the neurotransmitters serotonin and dopamine, low levels of melatonin are a frequently consistent observation in people suffering from depression. In the last decade, studies were conducted that have established a corollary link between the biosynthesis of melatonin in the penal gland and the nyctohemeral rhythms of SAMe.

SAMe's effectiveness as an anti-depressant is demonstrated in a plethora of clinical studies. The depth of many of these trials is also impressive, so much so that not only is SAMe legally registered as a recommendation drug in Italy, Germany, Spain and Russia, but even the extremely influential U.S. Department of Health stated that SAMe's effect on depression was 'clinically significant'. More notably, it did so without categorizing SAMe as a drug.

Studies
SAMe's anti-depressant activity is aptly demonstrated in many key human trials. One such trial in Italy in 1995 saw 195 patients being given 400 mg of SAMe (parenterally administered) for 15 days. Depressive symptoms remitted after both 7 and 15 days of treatment, and no serious adverse events were reported, testimony to the speed of SAMe's efficacy. Another study, this one in California a year earlier, directly compared SAMe with a tricyclic antidepressant called desipramine using 26 patients suffering from what was diagnosed as major depression. The two groups underwent treatment for four weeks, and at the conclusion of the study it was found that 62% of the SAMe patients had experienced significant improvement compared to the 50% of the desipramine patients who did so. 'Significant improvement' in this case was measured in accordance with the Hamilton Depression Rating Scale (HAM-D), a scientifically standardized method of measuring depression symptoms.

SAMe and Osteoarthritis
By a happy coincidence, many of the patients of the aforementioned SAMe trials for depression also noticed the simultaneous alleviation of their arthritic symptoms. In order to eliminate the possibility of attributing this to any residual placebo effect from the anti-depressant properties of SAMe, 10 studies were conducted specifically on osteoarthritis patients who were not diagnosed with depression. These studies involved a total of 22,000 participants in both Europe and the United States, and the general consensus from this massive collection of data is twofold. The first is that SAMe demonstrated clear efficacy in treating osteoarthritis compared to a placebo. The second is that SAMe possesses therapeutic effects similar to those of the standard non-steroidal anti-inflammatory agents (NSAIDs) used to treat osteoarthritis, but is better tolerated.

The mechanism of action for SAMe's treatment of osteoarthritis indicates an ability to increase the synthesis and proliferation of proteoglycans. Furthermore, SAMe may effectively protect proteoglycans from decomposition by proteolytic and glycotic enzymes by promoting the growth of polyamines as a stabilizing factor for the proteoglycans. SAMe may also elicit its benefits on osteoarthritis through an anti-inflammatory capability as well. Evidence pointing to this includes the fact that SAMe can restore the condition of cultured synovial cells after they have been exposed to the damaging effects of pro-inflammatory cytokines.

SAMe and Liver Health
The fundamental metabolism of SAMe itself goes a considerable way in explaining its effectiveness in treating hepatic conditions, including carcinogenic ones. The importance of glutathione as an omnipresent antioxidant cannot be understated, and unsurprisingly hepatic glutathione is one of the chief antioxidants involved in hepatic detoxification. Hepatic glutathione is dependent on methionine and SAMe metabolism for its own biosynthesis, and up to 80% of hepatic methionine is converted into SAMe. Studies have shown that patients with a wide etiology of liver disorders share the common denominator of being unable to metabolize methionine or SAMe effectively. In fact, subsequent studies have revealed that sufferers of chronic liver disorders do not have sufficient concentrations of a liver-specific isoenzyme identified as MAT I/III, which seems to play an essential role in the conversion of methionine to SAMe. Conversely, MAT I/III is vulnerable to high concentrations of nitric oxide and low levels of glutathione. Supplemental SAMe has been shown to increase glutathione concentrations in hepatic tissue as well as in red blood cells in general.