What is SAMe?

SAMe was first discovered in 1952 in Italy and has been commercially available to treat depression in Europe since 1976.
SAMe is short for S-adenosylmethionine (pronounced “Sammy”), a substance that occurs naturally in the body. It is the combination of one (1) essential amino acid, Methionine and ATP that plays a role in 35 – 40 biochemical reactions throughout the body.In most people, the body can make all the SAMe it needs, but some patients with depression and other conditions have been found to have lower levels of the compound as well as lower levels of Folic Acid (also known as Folate) and vitamin B12. These three (3) substances play a part in the metabolic process called “methyl donation” or “methylation”, a process in which a molecule made of one (1) carbon molecule and three (3) hydrogen atoms are attached to proteins and lipids.These methylation reactions are involved in the production of neurotransmitters (serotonin, dopamine and norepinephrine)in the brain and enzymes that help repair joints and the liver.

In the process of metabolizing SAMe, the independent coronary artery disease risk factor Homocysteine, which is a breakdown product of amino acid metabolism, is produced. Fortunately this Homocysteine is remethylized back into the “core” (Essential) amino acid Methionine. In this same cycle the body’s major antioxidant Glutathione is produced by means of a process known as “trans-sulphuration” and is mainly stored in the liver, hence the major antioxidant properties of SAMe.

Functions of SAMe in the body: (main)*
– Major antidepressant.
– liver detoxification (Glutathione effect).
– Mild osteoarthritic symptom relief, reputed to improve the quality of cartilage.
– Also used for fibromyalgia.
* for further information read the marketing brochure and the “Consumer information leaflet”.

How does SAMe work?

In the body, SAMe is what is called a “methyl donor”. This means that when SAMe reacts with Vitamin B12 and Folic Acid (Folate), it gives away units of carbon (a methyl group) to other molecules in the body. That process is critical in the production of depression fighting brain chemicals like serotonin.

Benefits & functions of SAMe

  • SAMe can increase levels of the important neurotransmitters (serotonin, norepinephrine, dopamine and phosphatdylserine) and increase the fluidity of brain cell membranes that effect the way in which brain cells receives and transmits messages via neurotransmitters such as these named above.
  • Research has shown that increased levels of SAMe can significantly enhance the body’s ability to detoxify itself of various substances and may actually help “mop up” old neurotransmitter material and improve the way fresh neurotransmitters bind to cells (an essential process for cells to communicate information).
  • Further, the effects of SAMe on the liver are impressive.SAMe promotes bile flow to aid the digestion of fat. SAMe also functions in the liver by preventing estrogens from causing damage to the liver. SAMe also assists the liver by increasing the production of glutathione which is the body’s major anti-oxidant.
  • Studies have also shown that a deficiency of SAMe in the joints can result in the loss of integrity. SAMe may help rebuild damaged cartilage and has been helpful for acute injuries and inflammation.
  • Under normal circumstances the body produces all the SAMe it needs from the amino acid methionine. However, a deficiency of methionine (the source of which is meat, fish and eggs), vitamin B6, Vitamin B12 or Folic Acid can result in diminished SAMe synthesis. In addition low levels of SAMe are not uncommon in the elderly and those experiencing joint related problems.

On a cellular level, whenever a SAMe molecule looses its methyl group, it breaks down into a compound called homocysteine, which is an amino acid – a molecule with the potential to wreak cellular havoc within our bodies.

High levels of homocysteine have the same effect on LDL cholesterols as does smoking which also oxidises the LDL and thereby
enables the LDL cholesterol to impregnate the coronary arteries and lay down plaque.

With the assistance of three B-Vitamins (Vitamin B6, Vitamin B12 and Folic Acid) our bodies convert homocysteine into the
valuable antioxidant glutathione through a process called transsulferation, or convert it back into methionine through remethylation.

When our bodies contain sufficient stores of these three B-Vitamins, homocysteine levels are kept comfortably low – but when our bodies are depleted of those vitamins, homocysteine levels can rise quickly, stalling the production of SAMe – potentially causing cellular damage and countless health problems.

  • SAMe has been confirmed by several studies to be as effective as the tricyclics (traditional pharmaceuticals) in the treatment of depression, with no, or minimal if any side effects reported.
  • SAMe is a naturally occurring compound that protects DNA from the genetic mutations associated with ageing and disease.
  • SAMe has also been used in Europe in the treatment of alcohol related liver damage and cirrhosis as well as damage caused by anaesthetics and viral hepatitis.
  • Methylation is a process that occurs a vast number of times per second in the body affecting everything from foetal development to brain function.
  • It regulates the expression of genes. It preserves the fatty membranes that insulate our cells. And it helps regulate the action of various hormones and neurotransmitters. And without SAMe there would be no methylation as we know it.

SAMe is the most active of all methyl-donors. Our bodies make it from methionine and then continually recycle it. Essentially, SAMe and homocysteine are two versions of the same molecule – one benign and one potentially dangerous when levels are too high.

We have learnt that when cells are well stocked with B-Vitamins, the brisk pace of methylation keeps homocysteine levels low.

But when we are low on those, homocysteine can build up quickly, stalling production of SAMe.

High homocysteine levels are possibly a major risk factor for heart attacks & strokes. During pregnancy it raises the risk of spina bifida and other birth defects.And many studies have implicated it in depression when levels are high and SAMe levels are low especially when the required folic acid, Vitamin B12 and Vitamin B6 are also low.

SAMe was first given to patients for use in treating depression, but when some of those patients began to report relief from osteoarhritis joint pain, researchers began to study this other possible benefit of the product.

Over 22,000 arthritis sufferers reported after only four weeks of treatment, that SAMe gave comparable results to NSAID (anti-inflammatory pain relievers) when used in higher dosages than required for treating depression ie more than 400mg per day.

2006 research ex Oxford and Rome universities predict increased cardiovascular disease risk in people using regular long term high dosages of NSAIDS.

The vital distinction is that instead of stomach-lining irritation that some NSAIDs can cause, SAMe may actually protect the stomach lining. Further more, animal studies show that SAMe could help restore damaged cartilage in addition to relieving pain.

How might taking extra SAMe improve a person’s mood?

Researchers have identified several possibilities. Normal brain functions involve the passage of chemical messengers between cells.

SAMe may enhance the impact of mood-boosting messengers such as dopamine and serotonin – either by regulating their breakdown or by speeding production of the receptor molecules they latch onto. SAMe may also make existing receptors more responsive.

These molecules float around in the outer membranes of brain cells like swimmers treading water in a pool.

If the membranes get thick and glutinous due to age and other assaults, the receptors loose their ability to move and change in response to chemical signals.

By methylating fats called phospolipids, SAMe keeps the membranes fluid and the receptors mobile.

Methylation reactions occur a vast number of times a second throughout our bodies. SAMe fuels these reactions by giving up its “methyl group.”KEY: C = Carbon H = Hydrogen N = Nitrogen O = Oxygen S = Sulfur
methionine 1. METHIONINETo make SAMe, we need methionine, an essential amino acid found in fish, meat and dairy products.Our bodies form SAMe by combining methionine with a substance called ATP.
3. SAH S-ADENOSYLHOMOCYSTEINEAfter giving up its methyl group, SAMe becomes SAH, which rapidly breaks down to form homocysteine.If homocysteine accumulates, it causes many health problems.
same molecule
2. SAME S-ADENOSYLMETHIONINEThe SAMe molecule readily donates its methyl group – the four atom appendage shown at the base of the diagram – to neighbouring molecules, that is methylation.
vitamin b12
4A. HOMOCYSTEINE REMETHYLATION
Our bodies can convert homocysteine back into methionine. This process requires Vitamin B12 and folic Acid, a B-vitamin found in fruits and vegetables.
4B. HOMOCYSTEINE TRANSSULFERATION
The body can also turn homocysteine into glutathione, a powerful antioxidant. This process, fueled by Vitamin B6 releases “sulfate groups” which help maintain cartilage.
The three primary reactions of SAMe in the body The main metabolic pathways involving SAMe

homocysteine amino acids