S-adenosylmethionine (SAM) is an important physiological compound produced in the body by combining the essential amino acid methionine with adenosyl triphosphate (ATP). SAM was discovered in Italy in 1952 and most of the research on its actions was done in this very country.

Food sources

Since SAM is a derivative of methionine, dietary sources of methionine might be thought to provide the same benefits as SAM. High doses of methionine, on the other hand, do not increase the levels of SAM and do not even have the same pharmacological activity, on the contrary they are accompanied by a certain toxicity.

Signs and symptoms of deficiency

The body usually produces all the SAM it needs from the amino acid methionine. However, a lack of methionine, vitamin B12 or folic acid can be the cause of a reduced synthesis of SAM.
Additionally, tissue SAM levels are typically low in the elderly and in patients with osteoarthritis, depression, and various liver diseases.

Beneficial effects

SAM is involved in over 40 biochemical reactions in the body. It works in close connection with folic acid and vitamin B12 in methylation reactions, the process in which a single carbon unit (methyl group) is added to another molecule. SAM is much more effective than other methyl donors at transferring methyl groups; methylation reactions are of critical importance for many components of the organism (especially in brain chemistry) and in detoxification reactions.
SAM is also needed in the synthesis of all sulfur-containing components of the body, including glutathione and various components of cartilage. The beneficial effects of SAM supplements are of great importance due to the central role played by this substance in many metabolic processes.

Forms available

SAM has been commercially available in Europe since 1975.

Main uses

There are five main diseases in which SAM is used: depression, osteoarthritis, fibromyalgia, liver disease and migraine.

Depression

SAM is necessary for the production of important substances in the brain, such as neurotransmitters, and phospholipids, such as phosphatidylcholine and phosphatidylserine. Supplementing the diet with SAM in depressed patients increases serotonin, dopamine and phosphatidylserine levels. It promotes the binding of neurotransmitters to receptor sites, which increases the activity of serotonin and dopamine and increases the fluidity of the brain cell membrane, all effects that cause significant clinical improvements.
The antidepressant action of folic acid is mild when compared to the effects seen in clinical trials with SAM. Based on the results of numerous clinical studies, it appears that SAM constitutes the most effective natural antidepressant (although valid evidence also exists in favor of hypericum extract standardized to contain 0.3% hypericin).
More recent studies, however, using a new oral preparation at a dose of 400 mg four times a day (1600 mg in total), show that SAM is effective in both oral and intravenous forms. SAM is better tolerated and manifests antidepressant action more quickly than tricyclic antidepressants.
The most recent study compared SAM with tricyclic desipramine. In addition to the clinical response, blood SAM levels were decisive in both groups. At the end of the 4-week trial, 62% of patients treated with SAM and 50% of those treated with desipramine had significant improvements. Regardless of the type of treatment, there was a significant increase in plasma SAM concentration in patients with a 50% reduction in the Hamilton depression score. These findings suggest that one of the pathways by which tricyclic drugs exert their antidepressant activity is by increasing SAM levels.
In addition to generalized depression, there are two other conditions accompanied by depression in which SAM achieves positive effects: the postpartum period and the recovery period of drug addicts. The benefits of SAM in these situations likely stem from the combination of its effects on brain chemistry and liver function. In a postpartum depression study , administration of SAM (1600 mg per day) significantly improved mood compared to placebo. Regarding drug detox use, SAM (1200 mg per day) significantly reduced the psychological stress (especially anxiety and depression) that accompanies drug addiction detoxification and rehabilitation.

Osteoarthritis

SAM has also achieved extraordinary results in the treatment of osteoarthritis. SAM deficiency in joint tissues, as well as glucosamine deficiency, leads to the loss of the gelatinous nature and shock absorbing properties characteristic of cartilage. As a result, osteoarthritis can develop. The drugs currently used in osteoarthritis (acetylsalicylic acid and other non-steroidal anti-inflammatory drugs) not only cause significant side effects, but by inhibiting cartilage repair and accelerating bone loss, they also promote the pathological process.
Natural compounds like SAM and glucosamine sulfate offer significant benefits over these popular drugs.
Many of the effects of SAM are very important in the treatment of osteoarthritis. First, SAM plays a central role in the synthesis of cartilage components and has been well documented in humans. In a double-blind study conducted in Germany, an increase in cartilage synthesis was observed in 14 patients with osteoarthritis of the hands who were treated with SAM, as evidenced by MRI. These results indicate that SAM is able to improve the structure and cartilage function of the joints affected by osteoarthritis. SAM has also shown some mild pain relieving and anti-inflammatory effects in animal studies. All of these effects combine to produce exceptional clinical benefits.
Overall, in careful clinical studies, 21524 patients with osteoarthritis used SAM. In double-blind clinical trials, SAM reduced pain indices and clinical symptoms in a similar way to non-steroidal anti-inflammatory drugs (ibuprofen, indomethacin, naproxen and piroxicam). Let's look at some of these studies.
In a double-blind study, SAM was compared to ibuprofen, a well-known drug. 36 subjects with osteoarthritis of the knee, hip and / or spine were given an oral dose of 1200 mg of SAM or 1200 mg of ibuprofen for a period of 4 weeks. Morning stiffness, pain at rest, pain with movement, crepitus (crackling noise produced by joint movement), swelling and limitation of movement in the affected joints were assessed before and after treatment. The total index, obtained from the evaluation of all individual clinical parameters, improved to the same extent in patients treated with SAM or ibuprofen. In two other studies, SAM produced slightly better results.
In several studies, SAM gave better results than naproxen. In a double-blind study, 20 patients with knee osteoarthritis were treated with either SAM or naproxen for 6 weeks. During the first week, SAM was administered at a dose of 400 mg three times a day, then at a dose of 250 mg twice a day. In the first two weeks, in case of severe pain, paracetamol was also associated as an additional analgesic. Patients were examined at the start of the study and after 2, 4, 6 weeks and the parameters considered were pain, crepitus, joint swelling, circumference of the joint, range of motion and time taken. to travel 10 meters. At the end of the sixth week,
Another double-blind study compared SAM with both naproxen and placebo in the treatment of osteoarthritis of the hip, knee, spine and hand. The study involved 33 rheumatology and orthopedic medical centers, for a total of 734 subjects. SAM administered orally at a dose of 1200 mg per day exerted the same analgesic (pain relieving) activity as naproxen at a dose of 750 mg per day. SAM, however, scored significantly better than naproxen by both physicians and patients; the number of patients who complained of side effects was also significantly lower. SAM was also better tolerated than placebo. Ten patients in the SAM group and 13 in the placebo group withdrew from the study due to drug intolerance.
Other double-blind studies indicate that SAM offers the same pain relieving and anti-inflammatory benefits as drugs such as indomethacin and piroxicam, but is generally better tolerated than these potent non-steroidal anti-inflammatories.

Perhaps the most significant investigation into SAM in the treatment of this condition is a long-term, multi-center, open, 2-year clinical study of 97 patients with osteoarthritis of the knee, hip and spine. These patients were given 600 mg of SAM per day (equivalent to three tablets of 200 mg each) until the end of the 24th month of treatment. The various locations of osteoarthritis (knee, hip, cervical vertebrae and dorsal-lumbar vertebrae) were examined separately. The severity of clinical symptoms (morning stiffness, pain at rest and with movement) was assessed by scores before the start of treatment, at the end of the first and second weeks, and then once a month until the end of 24 months. Administration of SAM showed good clinical efficacy and was well tolerated. The improvement of clinical symptoms during SAM therapy appeared already after the first weeks of treatment and continued until the end of the 24th month. Nonspecific side effects appeared in 20 patients, but in no case was it necessary to discontinue therapy. Most of the side effects disappeared during the course of therapy and no adverse effects were reported in the last 6 months of treatment. Accurate laboratory tests carried out at the beginning of the study and after 6, 12, 18 and 24 months of treatment did not give pathological results. The administration of SAM also improved the state of depression that is often associated with osteoarthritis. The improvement of clinical symptoms during SAM therapy appeared already after the first weeks of treatment and continued until the end of the 24th month. Nonspecific side effects appeared in 20 patients, but in no case was it necessary to discontinue therapy. Most of the side effects disappeared during the course of therapy and no adverse effects were reported in the last 6 months of treatment. Accurate laboratory tests carried out at the beginning of the study and after 6, 12, 18 and 24 months of treatment did not give pathological results. The administration of SAM also improved the state of depression that is often associated with osteoarthritis. The improvement of clinical symptoms during SAM therapy appeared already after the first weeks of treatment and continued until the end of the 24th month. Nonspecific side effects appeared in 20 patients, but in no case was it necessary to discontinue therapy. Most of the side effects disappeared during the course of therapy and no adverse effects were reported in the last 6 months of treatment. Accurate laboratory tests carried out at the beginning of the study and after 6, 12, 18 and 24 months of treatment did not give pathological results. The administration of SAM also improved the state of depression that is often associated with osteoarthritis. Nonspecific side effects appeared in 20 patients, but in no case was it necessary to discontinue therapy. Most of the side effects disappeared during the course of therapy and no adverse effects were reported in the last 6 months of treatment. Accurate laboratory tests carried out at the beginning of the study and after 6, 12, 18 and 24 months of treatment did not give pathological results. The administration of SAM also improved the state of depression that is often associated with osteoarthritis. Nonspecific side effects appeared in 20 patients, but in no case was it necessary to discontinue therapy. Most of the side effects disappeared during the course of therapy and no adverse effects were reported in the last 6 months of treatment. Accurate laboratory tests carried out at the beginning of the study and after 6, 12, 18 and 24 months of treatment did not give pathological results. The administration of SAM also improved the state of depression that is often associated with osteoarthritis. 18 and 24 months of treatment gave no pathological results. The administration of SAM also improved the state of depression that is often associated with osteoarthritis. 18 and 24 months of treatment gave no pathological results. The administration of SAM also improved the state of depression that is often associated with osteoarthritis.
Finally, in the largest study conducted, 20641 patients with osteoarthritis of the knee, hip and spine and osteoarthritic polyarthritis of the fingers were studied over a period of 8 weeks. Patients received 400 mg of SAM three times a day the first week, 400 mg twice a day the second week, and 200 mg twice a day the third week. No additional analgesic / anti-inflammatory treatment was allowed. The efficacy of SAM was comparable to that of non-steroidal anti-inflammatory drugs: very good or good in 71% of cases, moderate in 21% and poor in 9%. Tolerance was rated as good or very good in 87% of cases, moderate in 8% and poor in 5%.
All of these studies indicate that SAM offers significant advantages over non-steroidal anti-inflammatory drugs. While these drugs are associated with significant risks of toxicity and side effects and promote the pathological process of osteoarthritis, SAM offers significant benefits without risks or side effects.

Fibromyalgia

Fibromyalgia is a newly defined disease considered a common cause of chronic musculoskeletal pain and fatigue. Fibromyalgia has many things in common with another recently discovered syndrome, chronic fatigue syndrome. Regarding the diagnostic criteria, the only element that distinguishes the two pathologies is that musculoskeletal pain must be present in fibromyalgia and fatigue in chronic fatigue syndrome. Whether one diagnosis or the other is made depends on the specialization of the doctor one is addressing: if you consult a rheumatologist or orthopedic specialist, the diagnosis is much more likely to be fibromyalgia. In both pathologies the finding of an underlying depressive state is frequent.
Diagnosis requires compliance with all major criteria and at least four of the minor criteria. The major criteria are those listed below.

  • Generalized pain or stiffness in at least three anatomical sites for at least three months.
  • At least six characteristic points where pain can always be caused.
  • Exclusion of other diseases causing similar symptoms.

The minor criteria are as follows:

  • Generalized fatigue.
  • Chronic headache.
  • Sleep disorders.
  • Neurological and psychological disorders.
  • Joint swelling.
  • Feelings of numbness or tingling.
  • Irritable colon.
  • Symptom modification in relation to activity, stress and weather changes.

Three clinical studies show that SAM produces excellent benefits in fibromyalgia patients. The first double-blind, cross-sectional study was carried out on 17 patients with fibromyalgia. During treatment with SAM (one injection of 200 mg per day, for 21 days), subjects showed a significant reduction in the number of trigger points and tender points , as well as improvements in 'humor.
In another double-blind study, the administration of oral SAM (800 mg daily) for 6 weeks to 44 fibromyalgia patients was compared with placebo. The researchers evaluated the number of trigger points, muscle strength, disease activity, subjective symptoms, mood parameters and side effects. Improvement of clinical disease activity, pain over the last week, fatigue, morning stiffness and mood was observed in patients who received SAM; there were no differences, however, between the two groups regarding the number of "trigger" points and muscle strength. SAM caused no side effects.
The most recent study compared the effects of SAM and transcutaneous electrical nerve stimulation (a common therapy for fibromyalgia) in 30 patients with this condition. In patients who received SAM (200 mg by injection and 400 mg by mouth) the clinical benefits were significantly greater: decrease in the number of painful spots, reduction of subjective pain and fatigue sensation, improvement of mood. Transcutaneous electrical stimulation barely relieved most symptoms, while SAM was described as "effective in reducing the signs and symptoms of primary fibromyalgia."

Diseases of the liver

SAM is also quite useful in several liver diseases, including liver cirrhosis, Gilbert's syndrome and liver damage from oral contraceptives. The benefits are related to its function as the main methyl donor in the liver and its lipotropic activity.
SAM appears to be the perfect supplement to alleviate the condition that naturopathic doctors often refer to as "lazy liver".
This term is used to describe an alteration or impairment of liver function. Given the important role played by the liver in numerous metabolic processes, even mild liver failure can have significant consequences. One of the factors that contribute most to damage to liver function is the reduction in the flow of bile or cholestasis. SAM positively affects various liver disorders due to its ability to promote the flow of bile and reduce cholestasis.
Cholestasis can be caused by a number of factors, including obstruction of the bile ducts and obstruction of the flow of bile within the liver. The most common cause of bile duct obstruction is the presence of stones. Numerous factors or diseases can obstruct the flow of bile within the liver. Typically these diseases are accompanied by alterations in laboratory tests of liver function (serum bilirubin, alkaline phostatase, SGOT, LDH, GGTP etc.), indices of cell damage. However, relying solely on these tests to assess liver function is not always advisable; many of these early stage or "subclinical" diseases may have normal laboratory values ​​and liver dysfunction can only be assessed with expensive and / or invasive tests.
Currently, clinical judgment based on the patient's history remains the primary diagnostic tool for "lazy liver". People with this condition can complain of fatigue, general malaise, digestive disorders, allergies and hypersensitivity to chemicals, PMS and constipation. The causes of cholestasis are listed below.

  • Presence of gallstones
  • Alcohol
  • Endotossine
  • Hereditary diseases (Gilbert's syndrome)
  • Pregnancy
  • Natural and synthetic steroid hormones (anabolic steroids, estrogen, oral contraceptives)
  • Certain drugs or chemicals (aminosalicylic acid, chlorothiazide, mepazine, phenylbutazone, sulfadiazine, thiouracil)
  • Hyperthyroidism or thyroxine supplements
  • Viral hepatitis

A key function of SAM in the liver is estrogen inactivation. Clinical studies show that SAM is very effective in protecting the liver from estrogen damage and in improving its function when the quantity of these hormones increases greatly: for example in oral contraception, in pregnancy and in premenstrual syndrome.
SAM also has positive effects in the treatment of Gilbert's syndrome, a fairly common syndrome characterized by chronically elevated serum bilirubin levels (1.2 to 3.0 mg / dl). It was once considered a rare disease, but is now believed to affect at least 5% of the population. It is generally asymptomatic, although some patients complain of loss of appetite, malaise and fatigue (typical symptoms of impaired liver function). SAM, at a dose of 400 mg, three times a day, significantly reduced serum bilirubin values ​​in patients with Gilbert's syndrome.
In addition to these relatively mild disorders, SAM may also be useful in the treatment of more severe liver diseases such as liver cirrhosis, in which supplements appear to correct the SAM depletion characteristic of this pathology. SAM is involved in so many liver functions that its deficiency can have serious consequences. SAM supplements in patients with liver cirrhosis not only promote bile flow but also improve membrane function and increase glutathione levels. Glutathione plays a fundamental role in detoxification and defense against many harmful substances: it binds directly to toxic products and forms water-soluble compounds that are easily eliminated. Since many toxic substances are fat soluble, the transformation into water-soluble compounds favors a more rapid and effective excretion by the kidneys. In the presence of high levels of toxic compounds or when liver function is impaired, higher concentrations of glutathione are required.
One of the main risks of chronic liver disease, for example chronic hepatitis, is liver cancer. Supplements with SAM are particularly indicated in patients with these diseases to reduce this risk. Animal studies show a significant protective effect of SAM supplements against liver cancer in animals exposed to liver carcinogens.

Migraine

SAM is also useful in migraines. The benefits come on gradually and long-lasting treatment is required to achieve therapeutic efficacy.

Specific dosages

In general, the longer SAM is taken, the greater the benefits it brings. It is perfectly suited for long-term use due to its excellent safety profile. Here are some dosage ranges for the various clinical indications.

  • Depression: 400 mg 3-4 times a day. Since SAM can cause nausea and gastrointestinal upset in some individuals, it is best to start with a dose of 200 mg twice a day on the first day, then moving to 400 mg twice a day on the third day, to 400 mg three times a day on the day. 10th day, and finally, if necessary, at the full dose of 400 mg four times a day after 20 days.
  • Osteoarthritis: start out the same as for depression. After 21 days at a dose of 1200 mg per day, switch to the maintenance dose of 200 mg twice a day.
  • Fibromyalgia: 200-400 mg twice a day.
  • Liver disorders: 200-400 mg two or three times a day.
  • Migraine: 200-400 mg twice a day.

Warnings and Precautions

No side effects of orally administered SAM have been reported except, occasionally, nausea and gastrointestinal upset. In bipolar depression (alternation of mania and depression) the intake of SAM must take place under strict medical supervision: the antidepressant activity of SAM, in fact, can trigger the manic phase. However, this is an effect that occurs only in some individuals with bipolar depression.

Interactions

SAM works very closely with vitamin B12, folic acid, vitamin B6 and choline in methylation reactions. Due to its effects on the liver, it can increase the elimination of various drugs from the body. The clinical significance of this particular action is not yet fully understood.

Bibliography

Strementinoli G, Pharmacological aspects of S-adenosylmethionine: Pharmacokinetics and pharmacodynamics. Am J Med 83 (Suppl.5A), 35-42, 1987.
Bombardieri G, et al., Intestinal absorption of S-adenosyl-L-methionine in humans. Int J Clin Pharmacol Ther Toxicol 21, 186-188, 1983.
Baldessarini RJ, Neuropharmacology of S-adenosyl-L-methionine. Am J Med 83 (Suppl. 5A), 95-103, 1987.
Reynolds E, Carney M, and Toone B, Methylation and mood. Lancet ii, 196-199, 1983.
Bottiglieri T, Laundry M, Martin R, et al., S-adenosylmethionine influences monoamine metabolism. Lancet ii, 224, 1984.
Janicak PG, et al., Parental S-adenosylmethionine in depression: A literature review and preliminary report. Psychopharmacology Bulletin 25, 238-241, 1989.
Friedel HA, Goa KL, and Benfield P, S-adenosylmethionine. Drugs 38, 3389-3417, 1989.

Carney MWP, Toone BK, and Reynold EH, S-adenosylmethionine and affective disorder. Am J Med 83 (Suppl.5A), 104-106, 1987.
Vahora SA and Malek-Ahmadi P, S-adenosylmethionine in depression. Neurosci Biobehav Rev 12, 139-141, 1988.
Kagan BL, et al., Oral S-adenosylmethionine in depression: A randomized, double-blind placebo-controlled trial. Am J Psychiatry 147, 591-595, 1990.
Rosenbaum JF, et al., An open-label pilot study of oral S-adenosylmethionine in major depression. Psychopharmacol Bull 24, 189-194, 1988.
De Vanna M and Rigamonti R, Oral S-adenosyl-L-methionine in depression. Curr Ther Res 52, 478-485, 1992.
Salmaggi P, et al., Double-blind, placebo-controlled study of S-adenosyl-L-methionine in depressed postmenopausal women. Psychother Psychosom 59, 34-40, 1993.
Bell KM, et al., S-adenosylmethionine blood levels in major depression: Changes with drug treatment. Acta Neurol Scand 154, 15-18, 1994.
Cerutti R, et al., Psychological distress during puerperium: A novel therapeutic approach using S-adenosylmethionine. Curr Ther Res 53, 707-717, 1993.
Lo Russo A, et al., Efficacy of S-adenosyl-L-methionine in relieving psychological distress associated with detoxification in opiate abusers. Curr Ther Res 55, 905-913, 1994.
Brandt KD, Effects of nonsteroidal anti-inflammatory drugs on chondrocyte metabolism in vitro and in vivo. Am J Med 83 (Suppl. 5A), 29-34, 1987.
Shield MJ, Anti-inflammatory drugs and their effects on cartilage synthesis and renal function. Eur J Rheumatol Inflam 19, 7-16, 1993.
Brooks PM, Potter SR and Buchanan W, NSAID and osteoarthritis-help or hindrance. J Rheumatol 9, 3-5, 1982.
Newmann NM and Ling RSM, Acetabular bone destruction related to non-steroidal anti-inflammatory drugs. Lancet ii, 11-13, 1985.
Solomon L, Drug induced arthropathy and necrosis of the femoral head. J Bone Joint Surg 55B, 246-251, 1973.
Harmand MF, et al., Effects of S-adenosylmethionine on human articular chondrocyte differentiation: An in vitro study. Am J Med 83 (Suppl. 5A), 48-54, 1987.
Konig H, et al., Magnetic resonance tomography of finger polyarthritis: Morphology and cartilage signals after admetionin therapy. Aktuelle Radiol 5, 36-40, 1995.
Muller-Fassbender H, Double-blind clinical trial of S-adenosylmethionine versus ibuprofen in the treatment of osteoarthritis. Am J Med 83 (Suppl. 5A), 81-83, 1987.
Glorioso S, et al., Double-blind multicentre study of the activity of S-adenosylmethionine in hip and knee osteoarthritis. Int J Clin Pharmacol Res 5, 39-49, 1985.
Marcolongo R, et al., Double-blind multicentre study of the activity of S-adenosylmethionine in hip and knee osteoarthritis. Curr Ther Res 37, 82-94, 1985.
Domljan Z, et al., A double-blind trial of ademetionine vs naproxen in activated gonarthrosis. Int J Clin Pharmacol Ther Toxicol 27, 329-333, 1989.
Caruso I and Pietrogrande V, Italian double-blind multicenter study comparing S-adenosylmethionine, naproxen, and placebo in the treatment of degenerative joint disease. Am J Med (Suppl. 5A) 66-71, 1987.
Vetter G, Double-blind comparative clinical trial with S-adenosylmethionine and indomethacin in the treatment of osteoarthritis. Am J Med 83 (Suppl. 5A), 78-80, 1987.
Maccagno A, Double-blind controlled clinical trial of oral S-adenosylmethionine versus piroxicam in knee osteoarthritis. Am J Med 83 (Suppl. 5A), 72-77, 1987.
Konig B, A long-term (two years) clinical trial with S-adenosylmethionine for the treatment of osteoarthritis. Am J Med 83 (Suppl. 5A), 89-94, 1987.
Berger R and Nowak H, A new medical approach to the treatment of osteoarthritis: Report of an oper phase IV study with admetionine (Gumbaral). Am J Med 83 (Suppl. 5A), 84-88, 1987.
Tavoni A, et al., Evaluation of S-adenosylmethionine in primary fibromyalgia: A double-blind crossover study. Am J Med 83 (Suppl. 5A), 107-110, 1987.
Jacobsen S, et al., Oral S-adenosylmethionine in primary fibromyalgia: Double-blind clinical evaluation. Scand J Rheumatol 20, 294-302, 1991.
Di Benedetto P, Iona LG, and Zidarich V, Clinical evaluation of S-adenosylmethionine versus transcutaneous nerve stimulation in primary fibromyalgia. Curr Ther Res 53, 222-229, 1993.
Mazzanti R, et al., On the antisteatosic effects of S-adenosyl-L-methionine in various chronic liver diseases: A multicenter study. Curr Ther Res 25, 25-32, 1979.
Frezza M, et al., Oral S-adenosylmethionine in the symptomatic treatment of intrahepatic cholestasis: A double-blind placebo-controlled study. Gastroenterology 99, 211-215, 1990.
Adachi Y, et al., The effects of S-adenosyl-methionine on intrahepatic cholestasis. Jap Arch Int Med 33, 185-192, 1986.
Padova C, Tritapepe R, Padova F, et al., S-adenosyl-L-methionine antagonizes oral contraceptive-induced bile cholesterol supersaturation in healthy women: Preliminary report of a controlled randomized trial. Am J Gastroenterol 79, 941-944, 1984.
Frezza M, et al., S-adenosylmethionine counteracts oral contraceptive hepatoxicity in women. Am J Med Sci 293, 234-238, 1987.
Bombardieri G, Milani A., Bernardi L, and Rossi L. «Effects of S-adenosyl-L-methionine (SAMe) in the treatment of Gilbert's syndrome». Curr Ther Res 37, 580-585, 1985.
Angelico M, et al., Oral S-adenosyl-L-methionine (SAMe) administration enhances bile salt conjugation with taurine in patients with liver cirrhosis. Scand J Clin Lab Invest 54, 459-464, 1994.
Kakimoto H, et al., Changes in lipid composition of erythrocyte membranes with administration of S-adenosyl-L-methionine in chronic liver disease. Gastroenterolia Japonica 27, 508-513, 1992.
Loguercio C, et al., Effects of S-adenosyl-L-methionine administration on red blood cell cysteine and glutathione levels in alcoholic patients with and without liver disease. Alcohol Alcoholism 29, 597-604, 1994.
Pascale RM, et al., Chemoprevention of rat liver carcinogenesis by S-adenosyl-L-methionine: A long-term study. Cancer Res 52, 4979-4986, 1992.
Gatto G, et al., Analgesizing effects on a methyl donor (S-adenosylmethionine) in migraine: An open clinical trial. Int J Clin Pharmacol Res 6, 15-17, 1986.
Reicks M and Hathcock JN, Effects on methionine and other sulfur compounds on drug conjugations. Pharmac Ther 37, 67-79, 1988.