Depression, Folate, SAMe and serotonin

seroSAMe

S-Adenosylmethionine (SAMe) is a naturally-occurring compound found in almost every tissue and fluid in the body. It is involved in many important processes. SAMe plays a role in the immune system, maintains cell membranes, and helps produce and break down brain chemicals, such as serotonin, melatonin, and dopamine. It works with vitamin B12 and folate (vitamin B9). Being deficient in either vitamin B12 or folate may reduce levels of SAMe in your body.

Several studies show that SAMe helps relieve the pain of osteoarthritis. Other studies suggest that SAMe may help treat depression. Researchers have also examined SAMe’s use in the treatment of fibromyalgia and liver disease with mixed results. Many of the early studies used SAMe given intravenously or as an injection. Only recently have researchers been able to look at the effects of SAMe taken by mouth.

Depression

Some research suggests that SAMe is more effective than placebo in treating mild-to-moderate depression and is just as effective as antidepressant medications without the side effects (headaches, sleeplessness, and sexual dysfunction). In addition, antidepressants tend to take 6 to 8 weeks to begin working, while SAMe seems to begin more quickly. Researchers are not sure how SAMe works to relieve depression. But they speculate it might increase the amount of serotonin in the brain just as some antidepressants do.

Many studies have examined injectable forms of SAMe, not oral supplements. More research is needed to determine whether SAMe works for depression. Because serious depression is a dangerous illness, you should seek help from your doctor before taking SAMe or any supplement.

Osteoarthritis

A number of well-designed studies show that SAMe may reduce pain and inflammation in the joints, and researchers think it may promote cartilage repair. In several short-term studies (ranging from 4 to 12 weeks), SAMe supplements were as effective as nonsteroidal anti-inflammatory drugs (NSAIDs, such as ibuprofen and naproxen) in adults with knee, hip, or spine osteoarthritis, in lessening morning stiffness, reducing pain and swelling, improving range of motion, and increasing walking pace. Several studies also suggest that SAMe has fewer side effects than NSAIDs. Another study compared SAMe to celecoxib (Celebrex), a type of NSAID called a COX-2 inhibitor, and found that over time SAMe was as effective as celecoxib in relieving pain. Other studies show no differences in pain relief or tolerability between treatment with SAMe or habumetone over 8 weeks in people with knee osteoporosis.

Fibromyalgia

SAMe can be effective in reducing symptoms of fibromyalgia, including pain, fatigue, morning stiffness, and depressed mood. But most studies used an injectable form of SAMe. Among studies that examined doses of SAMe by mouth, some found it was effective at reducing these symptoms while others found no benefit.

Liver disease

People with liver disease often cannot synthesize SAMe in their bodies. Preliminary studies suggest that taking SAMe may help treat chronic liver disease caused by medications or alcoholism. A study of 123 men and women with alcoholic liver cirrhosis (liver failure) found that SAMe treatment for 2 years improved survival rates and delayed the need for liver transplants better than placebo. Other studies show that SAMe may help normalize levels of liver enzymes in people with liver disease. Studies in mice show that SAMe protects against and can also reverse liver damage. However, these studies have been small and of short duration. Larger and longer studies are needed to confirm these findings.

Dementia

Preliminary evidence suggests that SAMe may improve cognitive symptoms, such as the ability to recall information and remember words. Researchers suspect SAMe acts on regions of the brain that regulate gene expression of amyloid proteins, one of the hallmarks of Alzheimer disease.

Other

Some studies suggest SAMe can effectively inhibit cancer tumor cells. Other studies suggest that taking the drug levodopa (L-dopa) for Parkinson disease may lower the levels of SAMe in the body, which may contribute to depression and increase the side effects of L-dopa. However, researchers have also found evidence that taking SAMe may make L-dopa less effective. If you have Parkinson disease, do not take SAMe without talking to your doctor first.

Dietary Sources

SAMe is not found in food. It is produced by the body from the amino acid methionine and ATP which serves as the major energy source for cells throughout the body.

Available Forms

SAMe is available in tablets or capsules, which are more stable and may be more dependable in terms of the amount of SAMe in the pill. They should be stored in a cool, dry place, but not refrigerated. Tablets should be kept in the blister pack until you take them.

How to Take It

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.

Precautions

Because of the potential for side effects and interactions with medications, you should take dietary supplements only under the supervision of a knowledgeable health care provider.

Side effects may include dry mouth, nausea, gas, diarrhea, headache, anxiety, a feeling of elation, restlessness, and insomnia. Sweating, dizziness, and palpitations have also been reported. For this reason, you should not take SAMe at night.

Large doses of SAMe may cause mania (abnormally elevated mood). Start at a low dose and gradually increase it. DO NOT exceed recommended doses.

Pregnant and breastfeeding women should not take SAMe.

People with bipolar disorder (manic depression) should not take SAMe since it may worsen manic episodes.

SAMe should not be combined with other antidepressants without first consulting your doctor.

People taking SAMe may want to take a multivitamin that contains folic acid and vitamins B12 and B6.

Possible Interactions

If you are being treated with any of the following medications, you should not use SAMe without first talking to your health care provider.

Taking SAMe at the same time as these drugs may increase the risk of serotonin syndrome (a potentially dangerous condition caused by having too much serotonin in your body):

  • Dextromethorphan (Robitussin DM, other cough syrups)
  • Meperidine (Demerol)
  • Pentazocine (Talwin)
  • Tramadol (Ultram)

Antidepressant medications

SAMe may interact with antidepressant medications, increasing the potential for side effects including headache, irregular or accelerated heart rate, anxiety, and restlessness, as well as the potential fatal condition called Serotonin Syndrome, mentioned above. Some experts theorize that taking SAMe increases the levels of serotonin in the brain, and many antidepressants do the same. The concern is that combining the two may increase serotonin to dangerous levels. Talk to your doctor before using SAMe if you are taking any medications for depression or anxiety.

Levodopa (L-dopa)

SAMe may reduce the effectiveness of this medication for Parkinson disease.

Medications for diabetes

SAMe may reduce levels of blood sugar and may strengthen the effect of diabetes medications, which increases the risk of hypoglycemia (low blood sugar).


Serotonin

Serotonin (/ˌsɛrəˈtnn, ˌsɪərə/[6][7][8]) or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Biochemically derived from tryptophan,[9] serotonin is primarily found in the gastrointestinal tract (GI tract), blood platelets, and the central nervous system (CNS) of animals, including humans. It is popularly thought to be a contributor to feelings of well-being and happiness.[10]

Approximately 90% of the human body‘s total serotonin is located in the enterochromaffin cells in the GI tract, where it is used to regulate intestinal movements.[11][12] The serotonin is secreted luminally and basolaterally which leads to increased serotonin uptake by circulating platelets and activation after stimulation, which gives increased stimulation of myenteric neurons and gastrointestinal motility.[13] The remainder is synthesized in serotonergic neurons of the CNS, where it has various functions. These include the regulation of mood, appetite, and sleep. Serotonin also has some cognitive functions, including memory and learning. Modulation of serotonin at synapses is thought to be a major action of several classes of pharmacological antidepressants.

Serotonin secreted from the enterochromaffin cells eventually finds its way out of tissues into the blood. There, it is actively taken up by blood platelets, which store it. When the platelets bind to a clot, they release serotonin, where it serves as a vasoconstrictor and helps to regulate hemostasis and blood clotting. Serotonin also is a growth factor for some types of cells, which may give it a role in wound healing. There are various serotonin receptors.

Serotonin is metabolized mainly to 5-HIAA, chiefly by the liver. Metabolism involves first oxidation by monoamine oxidase to the corresponding aldehyde. This is followed by oxidation by aldehyde dehydrogenase to 5-HIAA, the indole acetic acid derivative. The latter is then excreted by the kidneys.

In addition to animals, serotonin is found in fungi and plants.[14] Serotonin’s presence in insect venoms and plant spines serves to cause pain, which is a side-effect of serotonin injection.[citation needed] Serotonin is produced by pathogenic amoebae,[citation needed] and its effect on the gut[specify] causes diarrhea.[citation needed] Its widespread presence in many seeds and fruits may serve to stimulate the digestive tract into expelling the seeds.


Folate Deficiency Signs and Symptoms

Loss of appetite and weight loss can occur. Additional signs are weakness, sore tongue, headaches, heart palpitations, irritability, and behavioral disorders.[3] In adults, anemia (macrocytic, megaloblastic anemia) can be a sign of advanced folate deficiency.

In infants and children, folate deficiency can slow growth rate. Women with folate deficiency who become pregnant are more likely to give birth to low birth weightpremature infants, and infants with neural tube defects.

Late studies suggested an involvement in tumorogenesis (especially in colon) through demethylation/hypomethylation of fast replicating tissues.

Some of the symptoms can also result from a variety of medical conditions other than folate deficiency. It is important to have a physician evaluate these symptoms so that appropriate medical care can be given.

Depression[edit]

Studies suggest that folate and vitamin B12 status may play a role in depression.[4] The role of vitamin B12 and folate in depression is due to their role in transmethylation reactions, which are crucial for the formation of neurotransmitters (e.g. serotonin, epinephrine, nicotinamides, purines, phospholipids).[4][5]

Low levels of folate or vitamin B12 can disrupt transmethylation reaction, leading to an accumulation of homocysteine (hyperhomocisteinemia) and to impaired metabolism of neurotransmitters (especially the hydroxylation of dopamine and serotonin from tyrosine and tryptophan), phospholipids, myelin, and receptors. High homocysteine levels in the blood can lead to vascular injuries by oxidative mechanisms which can contribute to cerebral dysfunction. All of these can lead to the development of various disorders, including depression.[4][5]

Low plasma B12 and low plasma folate has been found in studies of depressive patients. Furthermore, some studies have shown that low folate levels are linked to a poor response of antidepressant treatment, and other studies also suggest that a high vitamin B12 status may be associated with better treatment outcomes. Therefore, not only does adequate consumption of these two vitamins help decrease the risks of developing depression, but they can also help in the treatment of depression when antidepressant drugs are used

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