Sam-E and Sadness

What is SAM-e?

SAM-e is also known as S-adenosyl methionine or ademethionine. It is found in all the cells of the body where it is synthesized from an amino acid, methionine, and an energy molecule, adenosine triphosphate (ATP).

Although found everywhere, the liver is the major site of production and utilization of SAM-e in the body.

SAM-e is required for a number of important metabolic reactions in the body. Most of these reactions involve the transfer of methyl and sulfur groups from SAM-e to other compounds such as lipids, proteins, and nucleic acids.

After SAM-e is produced and utilized in the body, it is then regenerated in a cycle. Besides serving as a donor for other important molecules in the body, SAM-e is involved in cellular growth and repair.

SAM-e is also required for the production of hormones in the body as well as neurotransmitters in the brain. Because SAM-e increases the production of mood-enhancing neurotransmitters such as dopamine and serotonin, it is sometimes recommended as an antidepressant supplement.

As a nutritional supplement, SAM-e is prescribed in the treatment of depression, arthritis pain, and liver disease. SAM-e deficiency is also commonly found in people suffering from Alzheimer’s disease. However, there are indications that it is a vitamin B12 deficiency that is the root cause of the neurological damage attributed to SAM-e in the case of Alzheimer’s disease.

Because the production of SAM-e dwindles with age, its supplementation is sometimes advised for the elderly.

Oral SAM-e supplements are sold as salts and as enteric-coated tablets to help improve the absorption and stability of the drug. The oral supplement should also be taken on an empty stomach since it is more easily absorbed in the absence of food.

SAM-e: Side Effects and Dosage

SAM-e supplements have been known to cause gastrointestinal discomforts. Other side effects include heartburn, nausea, constipation, bloody stool, loss of appetite, dry mouth, sweating, increased urination, and anxiety.

SAM-e can also cause insomnia. Therefore, it should be taken in the morning rather than in the evening.

Even more serious side effects may result from increased homocysteine levels especially in individuals with B vitamin deficiencies. Vitamins B6, B9, and B12 are cofactors of SAM-e in different metabolic reactions. For example, every time SAM-e transfers methyl groups to choline, it is converted to a metabolite known as S-adenosyl-homocysteine which can be further converted to homocysteine.

Homocysteine is a toxic intermediate in metabolic reactions. It is usually converted to amino acids such as methionine and cysteine as well as antioxidant enzymes such as glutathione. However, when the levels of B vitamins are low, these conversions do not proceed and homocysteine accumulates in the body.

Although the risk of homocysteine accumulation from high doses of SAM-e is low, it still exists.

High levels of homocysteine can harden the arteries; increase the risk of stroke and heart disease, and cause liver damage and Alzheimer’s disease.

Uncommon adverse effects of SAM-e include the induction of mania in people suffering from bipolar (manic-depressive) syndrome; dangerously low blood sugar levels and abnormal insulin sensitivity in diabetics; and serotonin syndrome when combined with drugs that increase serotonin levels and/or activities in the brain.

Although the therapeutic doses of SAM-e range from 400 mg/day to 1,600 mg/day, most doctors prefer to prescribe at a lower dose range (50 – 200 mg/day) to reduce the risks of serious side effects.

SAM-e is also available as intravenous infusions and intramuscular injections. Medical supervision is required when giving these non-oral formulations of SAM-e in order to prevent and arrest any sudden serious side effects that may result.

How SAM-e Eases Sadness

The main mechanism by which SAM-e improves mood is by serving as a precursor in the syntheses of certain neurotransmitters in the brain.

When SAM-e is converted onwards to the amino acids or enzymes required in the production of these neurotransmitters, it indirectly increases the amount of the neurotransmitters available in the synaptic junctions between neurons.

More specifically, SAM-e increases the production of serotonin and dopamine in the brain.

Serotonin and dopamine are the two most important neurotransmitters to mood. By increasing the levels of these brain chemicals, it is possible to increase alertness, mental focus, good feelings and the perception of wellbeing. All of these are positive results in the treatment of depression.

Multiple studies have shown that SAM-e is definitely effective in this role. Most users report elevation of mood and eagerness to work and play within a few hours after taking this supplement.

Because SAM-e generally increases the syntheses of monoamine neurotransmitters, it can also increase the levels of stimulatory neurotransmitters such as epinephrine and norepinephrine. This may be responsible for the stimulation and alertness that informs the recommendation to take SAME-e in the morning and not before bedtime. When taken at night, SAM-e may cause insomnia.

There also some reports that the effect of SAM-e on neurotransmitter syntheses can also make it useful in controlling obsessive behaviors.

Habits such as gambling have been successfully controlled with SAM-e.

It is believed that by increasing the levels of certain neurotransmitters in specific parts of the brain, SAM-e can promote rational thinking and lift the mental fog that favors delusional thoughts.

This ability to control compulsive, destructive habits may contribute to or be another benefit of the antidepressant effects of SAM-e.

Besides increasing neurotransmitter levels in the brain, SAM-e can also boost energy production in brain cells, and serve as an antioxidant.

Since SAM-e is made from ATP, the chief energy molecule in cells, it can also release this molecule to improve the energy utilization of brain cells.

As an antioxidant, SAM-e protects brain tissue from the reactive oxygen species released from lipid peroxidation. In addition, it can also increase the levels of glutathione, a natural antioxidant that can mop up free radicals and protect cells from oxidative damage.

Studies on SAM-e and Depression

The Confirmatory Studies

A 1990 study published in The American Journal of Psychiatry investigated the effectiveness and safety of SAM-e in the treatment of depression. In this randomized, double-blind, placebo-control study, 15 patients with major depression were given oral SAM-e.

The results of the study showed that SAM-e was effective as an antidepressant. It also had a rapid onset of action; it was safe and produced only a few side effects.

The researchers confirmed that SAM-e was effective as an antidepressant because it was a methyl group donor. They also recommended the supplement for depressed patients who cannot tolerate standard antidepressants.

Another 1990 study also agreed with this conclusion. This other study was published in the journal, Acta Psychiatrica Scandinavica and it took a slightly different approach.

The researchers recruited 20 depressed patients for this study. Nine of these patients had already failed to respond to standard antidepressants while 11 of them were well controlled with these antidepressants.

After oral SAM-e supplementation, the researchers reported that all 20 patients with major depression experienced significant improvements. In addition, 7 out of the 11 patients with good histories of antidepressant responses were fully recovered from their depression.

For the non-responsive group, the SAM-e supplementation was able to get 2 of them to full recovery.

This study showed that SAM-e is comparable to standard antidepressants and that it can even help some depressed patients when standard antidepressants fail.

A review of the use of SAM-e in the treatment of depression was published in 2002 in the journal, Australian Family Physician.

The reviewers concluded that available clinical studies suggested that SAM-e was effective in the treatment of mild to moderate depression. They also agreed that it was a safe supplement and that doctors can recommend this alternative therapy to their depressed patients.

Lastly, the reviewers found no objections to prescribing SAM-e as a first-line treatment for depression.

The Complementary Studies

A 1992 study published in the journal, Psychiatry Research, investigated the possible benefits SAM-e may have on the onset of action of the antidepressant, imipramine.

Twenty four patients with moderate to severe depression were recruited for the active treatment phase of this trial. Over a period of 2 weeks, half of these patients were given 200 mg/day of SAM-e by intramuscular injection while the other group was given a placebo.

During the same period, all 24 patients were placed on 150 mg/day oral imipramine, and the onset of therapeutic response measured every other day.

At the end of the study, the researchers found out that the symptoms of depression decreased earlier in the group receiving the SAM-e plus imipramine.

This result suggests that SAM-e can improve the antidepressant effects of commonly recommended antidepressants. It also means that doctors can supplement the antidepressants they recommended for their patients with SAM-e either to achieve a faster onset of action or to treat non-responsive cases.

Another study published in 2004 in the Journal of Clinical Psychopharmacology investigated the usefulness of SAM-e as an adjunct drug in the treatment of a resistant major depressive disorder.

The study involved 30 patients with this disorder who were not responding to commonly effective antidepressants such as SSRIs (selective serotonin reuptake inhibitors) and venlafaxine. Each of these patients were given 800 – 1600 mg/day of the tosylate salt of SAM-e over the 6-week period of the trial.

The results of the study showed that half of the depressed patients responded to the combination of SAM-e and these standard antidepressants and that the introduction of the supplement significantly reduced the rate of remission.

The only side effects experienced with the addition of SAM-e were headache and gastrointestinal discomforts.

The researchers concluded that SAM-e was safe and effective in the augmentation of standard antidepressants such as the SSRIs and venlafaxine used in the study.

In HIV/AIDS Patients

HIV/AIDS can cause severe and prolonged depression in the individuals affected. In fact, depressive mood disorder is a major mental health complaint in such patients.

Given that HIV/AIDS patients already receive a cocktail of drugs, doctors prefer not to add standard antidepressants to their drugs. Instead, a safe and effective supplement such as SAM-e is much preferable. But is it effective in depressed HIV/AIDS patients?

In an open-label study undertaken by researchers from Community Research Initiative on AIDS (CRIA) and published in the journal, BMC Psychiatry, in 2004, 20 HIV-positive individuals with major depressive disorder were recruited for an 8-week study.

In the beginning, these study participants were given 200 mg of SAM-e two times daily along with 1,000 micrograms/day of vitamin B12 and 800 micrograms/day of folic acid. During the period of the study, the researchers increased the dosage of SAM-e as needed to a maximum of 800 mg twice daily.

At the end of the study, the median dose of SAM-e given was 400 mg twice daily.

The results of the study showed that SAM-e supplementation was safe and effective in the treatment of major depressive mood disorder in HIV/AIDS patients. In fact, the improvement was significant and was seen as early as the 1^st week of supplementation.

In addition, there were no reports of side effects from any of the study participants.

The addition of vitamin B12 and folic acid was important to increase the concentration of SAM-e in the brain. Low levels of vitamins, B6, B9 (folic acid) and B12 have been associated with low levels of SAM-e in the central nervous system.

In Pregnant and Lactating Women

A 1987 study published in the journal, International Clinical Psychopharmacology, investigated the effect of SAM-e supplementation on prolactin levels in depressed women.

This double-blind, placebo-controlled trial involved 20 participants with depression. Half of them were given SAM-e while the other half received a placebo. The levels of prolactin were measured before the study and also after the 14-day period of the trial.

The results showed that there was a very sharp reduction in prolactin levels of the SAM-e group.

This study indicates that the use of SAM-e should be restricted for pregnant and lactating women for reasons besides safety.

Prolactin is a hormone released from the pituitary gland. It is responsible for stimulating the growth and development of mammary glands as well as for increasing breast milk production after childbirth.

This study indicates that SAM-e use may reduce milk production in women. Therefore, physicians may need to weigh the merits and demerits of SAM-e supplementation in pregnant and lactation women who are also suffering from depression.