Human

SAMe is a molecule that is made naturally in the body from homocysteine and folate. It can also be made in a lab and taken in supplements.
SAMe is involved in the formation, activation, and breakdown of other chemicals in the body, including hormones, proteins, and certain drugs. The body uses it to make certain chemicals that play a role in pain, depression, liver disease, and other conditions.
People most commonly take SAMe for depression and osteoarthritis. It is also used for anxiety, liver disease, fibromyalgia, schizophrenia, and many other conditions.

SAMe in Depression:
Based on results from clinical studies it appears that SAMe is perhaps the most effective natural antidepressant. In fact, in these studies, SAMe has demonstrated better results than conventional antidepressant drugs with fewer side effects. In addition to generalized depression, SAMe also has been reported to produce significant effects in relieving postpartum (after pregnancy) depression and to reduce the anxiety and depression associated with drug detoxification and rehabilitation. Supplementing with SAMe in patients with depression is believed to improve mood via its ability to:
Raise levels of serotonin, dopamine, and phosphatidylserine.
Improve the binding of neurotransmitters to receptor sites, resulting in increased serotonin and dopamine activity.
Lead to better brain cell membrane fluidity and function.
Numerous double-blind studies have demonstrated a significant advantage of SAMe over a placebo in improving mood. It also compares favorably to conventional antidepressant drugs in terms of efficacy and is much better tolerated. The latest study with SAMe in depression indicates that it can be used with selective serotonin reuptake inhibitors (SSRIs) like Prozac, Zoloft, Paxil, etc. In a double-blind, randomized clinical trial lasting six weeks, 73 depressed patients unresponsive to SSRI medications, were given 800 mg of SAMe or placebo twice daily along with their SSRI. The Hamilton Depression Scale response and remission rates were higher for patients treated with SAMe (36.1% and 25.8%, respectively) than the placebo (17.6% versus 11.7%, respectively). The side effects were no different in the SAMe than the placebo group. These results indicate that SAMe can be used safely with SSRIs and may have a synergistic effect.

SAMe and Fibromyalgia:
Fibromyalgia is a common cause of chronic musculoskeletal pain, depression, and fatigue. SAMe has been shown in at least four clinical studies to produce excellent benefits in patients suffering from fibromyalgia. Improvements are noted by a significant reduction in the number of trigger points and painful areas as well as improvements in mood. SAMe appears to be a very important supplement in these patients.

SAMe and Liver disorders:
SAMe has been shown to be quite beneficial in several liver disorders including cirrhosis, Gilbert's syndrome, and oral contraceptive-induced liver damage. Its benefits are related to its function as the major methyl donor in the liver and promotion of detoxification reactions.
One of the key functions of SAMe in the liver is the inactivation of estrogens. Clinical studies have shown that SAMe is quite useful in protecting the liver from damage and improving liver function in conditions associated with estrogen excess - namely, oral contraceptive use, pregnancy and premenstrual syndrome.
SAMe has been shown to be quite helpful in the treatment of Gilbert's syndrome - a common syndrome characterized by a chronically elevated serum bilirubin level (1.2 to 3.0 mg/dL). Previously considered rare, this disorder is now known to affect as much as 5% of the general population. The condition is usually without symptoms, although some patients do complain about a loss of appetite, malaise, and fatigue (typical symptoms of impaired liver function). SAMe supplementation produces a significant decrease in serum bilirubin in patients with Gilbert's syndrome.
SAMe has also been shown to offer benefits in the treatment of more severe liver disorders including cirrhosis.

SAM cycleThe reactions that produce, consume, and regenerate SAM are called the SAM cycle. In the first step of this cycle, the SAM-dependent methylases (EC 2.1.1) that use SAM as a substrate produce S-adenosyl homocysteine as a product. S-Adenosyl homocysteine is a strong negative regulator of nearly all SAM-dependent methylases despite their biological diversity. This is hydrolysed to homocysteine and adenosine by S-adenosylhomocysteine hydrolase EC 3.3.1.1 and the homocysteine recycled back to methionine through transfer of a methyl group from 5-methyltetrahydrofolate, by one of the two classes of methionine synthases (i.e. cobalamin-dependent (EC 2.1.1.13) or cobalamin-independent (EC 2.1.1.14)). This methionine can then be converted back to SAM, completing the cycle. In the rate-limiting step of the SAM cycle, MTHFR (methylenetetrahydrofolate reductase) irreversibly reduces 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate.

Radical SAM enzymes
A large number of enzymes cleave SAM reductively to produce radicals: 5'-deoxyadenosyl 5'-radical, methyl radical, and others. These enzymes are called radical SAMs. They all feature iron-sulfur cluster at their active sites. Most enzymes with this capability share a region of sequence homology that includes the motif CxxxCxxC or a close variant. This sequence provides three cysteinyl thiolate ligands that bind to three of the four metals in the 4Fe-4S cluster. The fourth Fe binds the SAM.
The radical intermediates generated by these enzymes perform a wide variety of unusual chemical reactions. Examples of radical SAM enzymes include spore photoproduct lyase, activases of pyruvate formate lyase and anaerobic sulfatases, lysine 2,3-aminomutase, and various enzymes of cofactor biosynthesis, peptide modification, metalloprotein cluster formation, tRNA modification, lipid metabolism, etc. Some radical SAM enzymes use a second SAM as a methyl donor. Radical SAM enzymes are much more abundant in anaerobic bacteria than in aerobic organisms. They can be found in all domains of life and are largely unexplored. A recent bioinformatics study concluded that this family of enzymes includes at least 114,000 sequences including 65 unique reactions.[8]

Deficiencies in radical SAM enzymes have been associated with a variety of diseases including congenital heart disease, amyotrophic lateral sclerosis, and increased viral susceptibility.

Polyamine biosynthesis
Another major role of SAM is in polyamine biosynthesis. Here, SAM is decarboxylated by adenosylmethionine decarboxylase (EC 4.1.1.50) to form S-adenosylmethioninamine. This compound then donates its n-propylamine group in the biosynthesis of polyamines such as spermidine and spermine from putrescine.
SAM is required for cellular growth and repair. It is also involved in the biosynthesis of several hormones and neurotransmitters that affect mood, such as epinephrine. Methyltransferases are also responsible for the addition of methyl groups to the 2' hydroxyls of the first and second nucleotides next to the 5' cap in messenger RNA.

Starting with a low dose (for example, 200 mg per day) and increasing slowly helps avoid stomach upset.
It is important to note that many of the studies of SAMe have tested injectable, not oral, forms. It is not as clear whether taking SAMe orally is as reliable or effective. Small studies suggest that oral supplementation with SAMe is not well absorbed by the body. Clinicians recommend taking oral SAMe with vitamin B12, folic acid, methionine, and trimethylglycine to enhance absorption.

Pediatric
SAMe should never be given to a child without your doctor's supervision.

Adult
Recommended doses of SAMe vary depending on the health condition being treated. The following list gives information on the dosages used in studies for each condition:
Depression. 800 to 1,600 mg of SAMe per day, in 2 divided doses (morning and afternoon).
Osteoarthritis. 600 to 1,200 mg per day in 2 to 3 divided doses.
Fibromyalgia. A dosage of 400 mg, 2 times per day for 6 weeks.
Alcoholic liver disease. 600 to 1,200 mg per day by mouth in divided doses for 6 months enhances liver function. For liver disease, a qualified health care provider should supervise administration of SAMe.

We first need to talk about how mitochondria work. Your mitochondria are responsible for the energy metabolism of almost every cell in your body. They produce the bulk of energy needed for optimal health and performance. PQQ supports mitochondrial function, meaning it beneficially interacts with genes directly involved in mitochondrial health.
Lifestyle choices such as diet, sleep, stress and exercise can all affect mitochondrial health. Plus, your body is constantly being bombarded by environmental stressors. Supplementation with pyrroloquinoline quinone promotes youthful energy at the cellular level by keeping those mitochondria healthy-and supporting our mitochondrial proteins. Pyrroloquinoline quinone also supports the growth of new mitochondria and their proteins, a process known as mitochondrial biogenesis.

The wide array of PQQ's benefits are all derived from three primary functions that it provides

New Mitochondrial Growth
Mitochondria are the powerhouses of the cell and produce the vast majority of all cellular energy (ATP). PQQ activates a key transcription factor protein (CREB) and directly stimulates Mitochondrial Biogenesis, which is the growth and replication of new mitochondria. Stronger mitochondria, and more of them, produce more cellular ATP and thereby, users of PQQ may feel higher levels of natural energy.

Powerful Antioxidant
Antioxidants protect your cells from damage inflicted by harmful molecules called free radicals. PQQ is an extremely potent antioxidant and is approximately 100 times more effective than Vitamin C at reducing these free radicals. A continuous supply of PQQ provides long-lasting protection and promotes the longevity of your heart, brain, liver and other organs rich in mitochondria.

Nerve Cells Support
Nerve Growth Factor (NGF) is a small protein that plays a critical role in the growth, development and maintenance of neurons. PQQ has been found to promote NGF production, with one study showing as much as a 40x increase. Increased levels of NGF help to maintain the health of the brain and peripheral nerves while also stimulating nerve regeneration. This promotes more mental energy, greater focus, and better short-term memory.

As a powerful antioxidant, a stimulator of mitochondrial biogenesis and a trigger of Nerve Growth Factor production, PQQ is a triple threat to cellular aging.