Supplement SAMe

What is the supplement, SAMe?

SAMe is a naturally occurring compound that has so many roles in your body that it is essential to health and wellbeing.

S-Adenosyl methionine (SAMe) was first discovered in 1952 by Giulio Cantoni. It is a compound in the body (a sulphonium betaine) with a whole raft of interactive relationships that make it crucial for many functions in different systems, including multiple cellular reactions. SAMe is essential for cellular growth and repair, and therefore plays multiple roles in supporting health and longevity.

SAME is the biologically active metabolite of the sulphur-containing amino acid methionine and is formed from adenosine triphosphate (ATP) and L-methionine, with most of it being produced and utilised in the liver. It is the regulator of many vital processes in humans including DNA, RNA, methylation, the immune response, amino acid metabolism, sulphur pathways and phospholipids (particularly choline) among others. SAMe is the most widely used enzyme substrate in the body after ATP. In plants it is an important hormone and signalling molecule.

Methylation-dependent cycles are exquisitely sensitive to SAMe depletion from different diets or under stress conditions.

SAMe is most abundant in the liver, and a common product of SAMe metabolism is S-Adenosyl-L-homocysteine (SAH) which metabolises to homocysteine and adenosine. However, if SAH builds up in the system, the many SAMe-dependent methylation reactions are strongly inhibited by its accumulation.

Therapeutic uses

Liver and immune system

SAMe is most abundant in the liver, where it is a vital metabolite that regulates hepatocyte proliferation, necrosis and differentiation.

Innate immunity and lipogenesis are linked to adequate levels of phosphatidyl choline (PC), and a deficiency of PC is closely associated with the development of fatty liver disease — a common problem today. SAMe is critical for the maintenance and activity of PC in the liver.

With its important role in the synthesis of glutathione and with SAMe’s synthesis being suppressed in chronic liver disease, supplementing with this nutrient can improve outcomes in chronic liver diseases such as fatty liver and both alcoholic and non-alcoholic cirrhosis.

Research data suggests that low levels of serotonin in some depressed patients may in fact be a secondary consequence of low levels of SAMe.

Alcohol has a significant impact on SAMe and liver function. Low levels of SAMe reduces the ability of the liver to manage oxidative stress and worsens liver injury from any source, such as alcohol consumption, viral hepatitis, septic shock and toxin exposure. Rat studies showed depletion of SAMe resulted in spontaneous hepatocellular carcinoma, with supplementation correcting the disease. SAMe taken with betaine was shown to be the most effective in reducing liver cancer.

A clinical trial was conducted with hospitalised inpatients with chronic liver disease that included high bilirubin and high alkaline phosphatase and symptoms of fatigue, malaise and uncontrolled itching, a condition called intrahepatic cholestasis. A daily dose of 1600mg of SAMe was effective in reversing this condition, with minimal side effects.


Epigenetic changes are inherited alterations in DNA methylation that affect gene expression and function. This is influenced significantly by diet. A combination of environment and genetic environmental interactions modulates brain development. SAMe, as the principal methyl donor in cells, is critical for healthy brain and body development. As such it is showing promise in the treatment of multiple neuropsychiatric diseases such as Alzheimer’s disease, foetal alcohol syndrome and major depressive disorders.


SAMe is critical in the synthesis of hormones and neurotransmitters. A folate deficiency is common in depression, and this is known to lower levels of SAMe, the antidepressant nutrient that raises brain serotonin levels. Research data suggests that low levels of serotonin in some depressed patients may in fact be a secondary consequence of low levels of SAMe.

Anticancer and cardiovascular disease

Abnormal DNA methylation is a contributing factor in the development of human cancers and cardiovascular disease. Cancer, for example, is a process of whole-body undermethylation, which increases specific oncogene expression, and local hypermethylation at the tumour sites, which reduces tumour suppressor genes. Polyphenols such as flavonoids in tea, fruit and soy are potent inhibitors of hypermethylation, while folates, found in high concentrations in green leafy vegetables, regulate DNA methylation through their ability to generate SAMe. Individuals with the lowest level of folate as well as SAMe have significantly increased risk of developing several cancers and/or cardiovascular disease.


Viperin is an interferon-stimulated antiviral protein that restricts the infectivity of a wide range of viruses. It is a radical SAMe-dependent enzyme found in all forms of life. Viperin is possibly an ancient defence mechanism against viral infections that works by downregulating the metabolic pathways responsible for viral replication.


While the research has been inconclusive, SAMe may mitigate the pain of osteoarthritis, and studies have shown some improvement in pain and function after taking it for three months.

Cautions and contraindications

While SAMe is known to be generally safe, it can cause gastrointestinal upsets, dyspepsia and/or anxiety in sensitive individuals. It can also contribute to insomnia, so is best if taken in the morning.

Taken with SSRI medication, SAMe may contribute to serotonin syndrome. It may also exacerbate the side effects of antidepressant medication and reduce the therapeutic effect of levodopa in Parkinson’s patients. Do not take SAMe if you are on these medications unless under the guidance of a practitioner.

Dr Karen Bridgman

Dr Karen Bridgman

Karen Bridgman is a holistic practitioner at Lotus Health and Lotus Dental in Neutral Bay.

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