There are a number of substances in the body that are directly involved in metabolism and enzymatic reactions. Many of them are found in most tissues and fluids. Some of these substances are called methyl donors, and their main role is to donate methyl groups to other molecules in the body, which helps speed up metabolic processes or their retention. Many processes in the body depend on methylation. Such are the processing of lipids and the formation of DNA. One of the most powerful methyl donors in our bodies is S-Adenosylmethionine, a substance that is often deficient.
What is SAMe?
S-Adenosylmethionine is a completely natural substance that is found in almost every tissue in the human body. In essence, SAMe is the amino acid methionine linked to the molecule adenosine triphosphate (ATP). SAMe circulates in the blood and serves primarily as a methyl donor. SAMe is also known as ademethionine.
For unknown reasons, SAMe has a different metabolism in men and women. The concentration of SAMe in the blood of men is significantly higher. On the other hand, oral administration in women leads to faster and larger peaks in blood plasma. The current explanations are based on the fact that the initial concentration in the blood also affects the effectiveness of oral administration.
SAMe exists in two different forms – S / S and R / S. Both are thought to have high stability and bioactivity, but their functions differ significantly. Most studies have found that the real S / S is the bioactive form of methylation, while the R / S form even inhibits the function of the enzyme methyltransferase. So far, only one study has observed that over time, the S / S form depletes and becomes less active, but even the authors suggest that this is a possible rather than a reliable mechanism.
SAMe is characterized by extremely low oral activity. It was found that SAMe in capsules without special coating is absorbed within 0.5-1%, and in special capsules the absorption increases to 2-3%. The reason is the difficult passage through the small intestine.
Despite the low absorption through the intestinal tract, high single doses successfully increase the serum concentrations of the substance. Doses of 400 to 1000 mg on healthy individuals have been used for this purpose. A higher dose leads to a higher increase in concentrations and a longer half-life of the substance (1.7 to 6 hours). Eating on an empty stomach also has a positive effect on levels. Even regular intake of high doses of 1000 mg for several days does not change serum levels, which means that there is no rapid decline in the potency of orally administered SAMe.
Although SAMe has been sold as a dietary supplement since 1999, it was previously a popular medicine in the 1970s and 1980s, mostly in European countries such as Germany, Italy and Spain.
How does SAMe work?
S-Adenosylmethionine is involved as a methyl donor in the biosynthesis of hormones , neurotransmitters, DNA, proteins and phospholipids.
SAMe has the ability to cross the blood-brain barrier, and its high efficiency in many metabolic processes is due to the fact that SAMe uses its own transporter in the body, which is called SAMC.
One of the main functions of SAMe is related to its interaction with coenzymes in the body, as it is directly involved in the metabolism and functions of vitamin B-9. In the body, folic acid is converted to its bioactive form 5-methyltetrahydrofolate, which in turn transforms circulating homocysteine into methionine. This methionine binds to ATP molecules and forms SAMe, which after performing its functions as a methyl donor is converted into S-Adenosylhomocysteine. Homocysteine is formed from it again and the cycle is repeated. The relationship between the coenzyme form of vitamin B-9 and SAMe is that increased levels of SAMe lead to an increase in the amount of coenzyme B-9.
SAMe deficiency is not uncommon and occurs in some specific health conditions. It is not clear whether low levels of SAMe alleviate pathological conditions or whether the latter regulate the concentrations of the substance. It has been found that low levels of SAMe are found in individuals with depression, dementia, HIV-positive. It is interesting to note that the lowest levels are in patients with pneumonia. Observations in patients with kidney problems resulting from Type 1 Diabetes have shown that the exchange between coenzyme B-9 and SAMe is impaired, with levels of both substances below the critical minimum.
In other diseases, the opposite effect occurs and excessively high levels of S-adenosylmethionine are found. Such are schizophrenia and vitamin B-12 deficiency.
Potential and proven benefits in humans
- SAMe has been shown to have a positive effect on mood in humans, but its effectiveness against major depression is conditional. In fact, a direct link has been found between low levels of SAMe and coenzyme B-9 and the onset of depression. SAMe alone improves the condition in depression, but at high doses of 1600-3200 mg, within 12 weeks. In terms of effectiveness, SAMe is equivalent to antidepressants such as eskitalopram (SSRI) and tricyclic drugs. In addition to the effect alone, SAMe potentiates the effects of SSRI-type antidepressants (serotonin reuptake inhibitors), including in people who do not respond to drugs or respond partially;
- 800 mg per day SAMe improves quality of life and regulates aggression in patients with schizophrenia with low-activity COMT, an enzyme associated with aggressive behavior. Scientists have linked increased COMT activity to enhanced methylation processes;
- SAMe significantly improves depressive condition in Parkinson’s disease. Various doses of 800 to 3200 mg daily for 10 weeks have been used;
- SAMe demonstrated positive results in cognitive tests. Intake of 800 mg, twice daily, by healthy individuals demonstrates an increase in phosphocreatine levels of nearly 10%. The stimulating effect on brain activity is comparable to that of creatine. Improvement of cognitive processes is also observed in patients with cognitive deficits in major depression, but the results are significantly weaker than in healthy individuals. The results in adult but healthy patients are mixed, with some experiencing drowsiness and decreased activity;
- Serum concentrations of SAMe and coenzyme B-9 are related to blood flow and muscle function. High levels of SAMe are associated with improved blood supply;
- Although associated with methylation, SAMe did not significantly affect homocysteine. Tests to date have found no effect, except in a few cases in patients with high homocysteine, in whom SAMe intake resulted in a 19% reduction;
- In preliminary tests, SAMe showed positive results in fibromyalgia. Both intravenous and oral administration have been shown to be effective. A daily dose of 800 mg leads to a significant improvement in muscle pain, morning stiffness and muscle fatigue . There is an overall improvement in the health and quality of sleep. According to a small comparative study, SAMe reduces the symptoms of fibromyalgia more effectively than nonsteroidal anti-inflammatory drugs, but less well than serotonin reuptake inhibitors;
- It is used successfully in fatty liver and cirrhosis. The mode of action was associated with an increase in hepatic concentrations of glutathione and an increase in methylation processes. A large study in patients with cirrhosis found that taking 1200 mg of SAMe over 2 years reduced the rate of transplants and deaths from 29% to 12%. S-adenosylmethionine also has a positive effect on liver enzymes in intoxication and chemotherapy;
- The positive effect of SAMe on the liver has also been linked to the condition of cholestasis in pregnant women, in which bile cannot pass from the liver to the intestines and leads to liver damage. SAMe successfully reduces serum bile levels and liver enzymes , but performs worse than the drug ursodeoxycholic acid (UDCA);
- SAMe alone has no effect on the development of the Hepatitis C virus, but the addition to standard therapies may enhance their effect due to its methylating properties;
- SAMe is a substance closely related to the metabolism of vitamin B-9 (folate, folic acid ). It has been found that in cognitive deficits, due to a lack of vitamin B-9, SAMe may temporarily reduce symptoms, but does not lead to increased levels of vitamin B-9;
- SAMe is one of the most popular means of preventing osteoarthritis. A large study in patients with osteoarthritis of the knee and thigh used a daily dose of 1200 mg of SAMe for 30 days. There is an improvement in the condition, which is expressed in easier getting up from a sitting position, reducing movement restrictions and pain. After the fifteenth day, SAMe showed better results than the drug Naproxen. Another study found that SAMe was as effective as Selecoxib in terms of pain, swelling and movement restrictions. SAMe showed similar results compared to non-steroidal anti-inflammatory drugs and another drug such as Nabumetone, but in contrast, the effect was slower and the results appeared at the earliest after 30 days of use.
Potential and proven benefits in animals
- Studies in mice and monkeys have shown a direct link between SAMe intake and acetylcholine levels in the brain, through several mechanisms. First, SAMe enhances the conversion of nicotinamine to n-methyl-nicotinamide, which in turn prevents the extraction of choline from the brain and neurons. The second mechanism is related to the increase in the density of acetylcholine receptors;
- Some in-vitro and animal studies have found a link between the methylating properties of SAMe and testicular function. The use of S-adenosylhomocysteine reduces luteinizing hormone-induced androgen production by nearly 48%, while S-adenosylmethionine increases it by 28%. In turn, testosterone itself has a positive effect on the metabolism of SAMe and its activity in the body, suppressing the action of enzymes that break down SAMe. The interaction between testosterone and SAMe has yet to be studied in humans due to the lack of any observations.
SAMe is considered a relatively safe and non-toxic substance.
At the recommended doses, some mild and typical side effects such as nausea and stomach and abdominal discomfort may occur. Some individuals experience side effects such as sleep problems, sweating and loss of appetite.
SAMe is not recommended for use in pregnant or lactating women due to a lack of evidence of safety. SAMe is considered a safe substance for children, but only when administered intravenously, not orally.
SAMe can have some side effects in mental disorders. So far, there has been only one case in the treatment of depression in which SAMe has triggered mania attacks. This effect can also occur in bipolar disorder.
SAMe may worsen Parkinson’s disease when combined with other medicines or levodopa.
Due to the effect of SAMe on the central nervous system, it is not recommended to take before and after surgery.
There are insufficient data on long-term side effects at this stage.
High doses of 1000 mg per day are completely safe. It has been found that SAMe does not accumulate in the body and excess amounts are easily eliminated from the body. Even long-term use does not show side effects.
The recommended daily dose varies between 600 and 1200 mg, divided into doses of 2-3 times. In order to show the effect in arthritis, it is recommended to take it for at least a month. The effect in depressive states manifests itself much earlier.
With what to combine S-Adenosylmethionine?
As an additive SAMe can be used to treat arthritis or other joint diseases. For this purpose it can be combined with other anti-inflammatory substances such as bromelain , serapeptase, methylsulfonylmethane.
As a liver detoxifier, SAMe can be combined with n-acetyl cysteine, donkey thistle and curcumin.
SAMe successfully affects cognitive function and acetylcholine in the brain. As a brain stimulant, SAMe is combined with DMAE, Creatine, Alpha-GPC and Acetyl L-Carnitine.
The combination of SAMe with drugs such as antidepressants and MAO inhibitors is not recommended. Taking SAMe with levodopa (or mucuna) is not recommended because it may worsen brain function or Parkinson’s symptoms.
Where to find S-Adenosylmethionine?
SAMe is sold as a dietary supplement and as a medicine (Transmethyl).
As a dietary supplement, SAMe is sold only in the form of capsules, in most cases with a special coating. Variants of powder and ampoules can also be found as a medicine.
Rarely, S-Adenosylmethionine is used in complex formulas due to its high cost and high effective dose. In most cases, products with a concentration of up to 400 mg per capsule / tablet are available, and lower concentrated variants with doses of 100 mg and 200 mg per capsule / tablet are found.