SAMe for Osteoarthritis and Fibromyalgia Support

S-adenosylmethionine is quite a mouthful; the abbreviation SAMe (pronounced samm-ee) is easier to say. Its chemical structure and name are derived from two materials you may have heard about already: methionine, a sulfur-containing amino acid; and adenosine triphosphate (ATP), the body’s main energy molecule.

SAMe was discovered in Italy in 1952. It was first investigated as a treatment for depression, but along the way it was accidentally noted to improve arthritis symptoms—a kind of positive side effect.

Sources

The body makes all the SAMe it needs, so there is no dietary requirement. However, deficiencies in methionine, folate, or vitamin B12 can reduce SAMe levels. SAMe is not found in appreciable quantities in foods, so it must be taken as a supplement.

It’s been suggested that the supplement trimethylglycine (TMG) might indirectly increase SAMe levels and provide similar benefits, but this effect has not been proven.

Therapeutic Dosages

A typical full dosage of SAMe is 400 mg taken 3 to 4 times per day. If this dosage works for you, take it for a few weeks and then try reducing the dosage. As little as 200 mg twice daily may suffice to keep you feeling better once the full dosage has “broken through” the symptoms.

However, some people develop mild stomach distress if they start full dosages of SAMe at once. To get around this, you may need to start low and work up to the full dosage gradually.

Recently, SAMe has come on the US market at a recommended dosage of 200 mg twice daily. This dosage labeling makes SAMe appear more affordable (if you’re only taking 400 mg per day, you’ll spend only about a third or a fourth of what you’d pay for the proper dosage), but it is unlikely that SAMe will actually work when taken at such a low dosage.

Therapeutic Uses

A substantial amount of evidence suggests that SAMe can be an effective treatment for osteoarthritis, the “wear and tear” type of arthritis that many people develop as they get older.¹

A moderate amount of evidence suggests that SAMe might be helpful for depression.²

Weak and inconsistent evidence hints that SAMe might be helpful for a variety of liver conditions such as cirrhosis, chronic viral hepatitis, pregnancy-related jaundice, and Gilbert’s syndrome.^3-10,65-68

SAMe may help the painful muscle condition known as fibromyalgia.^11,12

SAMe has undergone some investigation as a possible supportive treatment for Parkinson’s disease. One study suggests that it may reduce the depression so commonly associated with the disease.¹³ In addition, the drug levodopa, used for Parkinson’s disease, depletes the body of SAMe.^14,15 This suggests that taking extra SAMe might be helpful. However, it is also possible that SAMe could interfere with the effect of levodopa, requiring an increase in dosage.

Highly preliminary evidence suggests that SAMe can protect the stomach against damage caused by alcohol.¹⁶

What Is the Scientific Evidence for S-Adenosylmethionine?

Osteoarthritis

• A substantial body of scientific evidence supports the use of SAMe to treat osteoarthritis.¹⁷ Double-blind studies involving a total of more than 1,000 participants suggest that SAMe is about as effective as standard anti-inflammatory drugs. In addition, animal evidence suggests that SAMe may help protect cartilage from damage.^18,19
• For example, a double-blind, placebo-controlled Italian study tracked 732 people taking SAMe, naproxen (a standard anti-inflammatory drug), or placebo.²⁰ After 4 weeks, participants taking SAMe or naproxen showed about the same level of benefit as compared to each other, and a superior level of benefit as compared to those in the placebo group.
• A more recent double-blind study compared SAMe to celecoxib (Celebrex), a member of the newest class of non-steroidal anti-inflammatory drugs.⁶⁴ Celecoxib produced more rapid effects than SAMe, but over time SAMe appeared to catch up. However, the lack of a placebo group makes these results less than fully reliable.
• Another double-blind study compared SAMe with the anti-inflammatory drug piroxicam.²¹ A total of 45 individuals were followed for 84 days. The two treatments proved equally effective. However, the SAMe-treated individuals maintained their improvement long after the treatment was stopped, whereas those on piroxicam quickly started to hurt again.
• Similarly long-lasting results have been seen with glucosamine and chondroitin. This pattern of response suggests that these treatments are somehow making a deeper impact on osteoarthritis than simply relieving symptoms. However, while we have some direct evidence that glucosamine and chondroitin can slow the progression of osteoarthritis, the evidence regarding SAMe is more hypothetical.
• In other double-blind studies, oral SAMe has shown equivalent benefits to various doses of indomethacin, ibuprofen, and naproxen.^22-24

Depression

• The evidence for SAMe for the treatment of depression provocative but far from definitive.
• Several double-blind, placebo-controlled studies have found SAMe effective in relieving depression, but most were small and poorly reported, and many used an injected form of the supplement.^25,26 Furthermore, the most recent trial, a double-blind, placebo-controlled study of 133 depressed patients, failed to find intravenous SAMe more effective than placebo. Researchers resorted to questionable statistical manipulation of the data to show benefit.²⁷
• Other trials compared SAMe to standard antidepressants rather than to placebo. The best of these was a 6-week, double-blind trial of 281 people with mild depression that compared oral SAMe to imipramine.²⁸ The results indicated that the two treatments were about equally effective. However, the absence of a placebo group makes this study less than fully definitive.
• Other studies have also compared the benefits of oral or intravenous SAMe to those of tricyclic antidepressants and have also found generally equivalent results; however, again, poor reporting and inadequacies of study design (such as too limited a treatment interval) mar the meaningfulness of the reported outcomes.^29-34,63

Fibromyalgia

• Four double-blind trials have studied the use of SAMe for fibromyalgia,^43-46 three of them finding it to be helpful. Unfortunately, most of these studies used SAMe given either intravenously or as an injection into the muscles, sometimes in combination with oral doses. When you inject a medication, the effects can be quite different than when you take it orally. For that reason, these studies are of questionable relevance.
• Nonetheless, the one double-blind study that used only oral SAMe did find positive results.⁴⁷ In this trial, 44 people with fibromyalgia took 800 mg of SAMe or placebo for 6 weeks. Compared to the group taking placebo, those taking SAMe had improvements in disease activity, pain at rest, fatigue, and morning stiffness, and in one measurement of mood. In other respects, such as the amount of tenderness in their tender points, the group taking SAMe did no better than those taking the placebo.
• It isn’t clear whether SAMe is helping fibromyalgia through its antidepressant effects, or by some other mechanism.

Parkinson’s Disease

• Evidence suggests that levodopa (the drug used to treat Parkinson’s disease) can reduce brain levels of SAMe.^48-50 This depletion may contribute to the side effects of levodopa treatment, as well as the depression sometimes seen with Parkinson’s disease. One study found that SAMe taken orally improved depression without changing the effectiveness of levodopa.⁵¹ However, it is also possible that over time taking extra SAMe could interfere with levodopa’s effectiveness. (See Safety Issues.)

Safety Issues

SAMe appears to be quite safe, according to both human and animal studies.^52-56 The most common side effect is mild digestive distress. However, SAMe does not actually damage the stomach.⁵⁷

Like other substances with antidepressant activity, SAMe might trigger a manic episode in those with bipolar disease (manic-depressive illness).^58-60

Safety in young children, pregnant or nursing women, or those with severe liver or kidney disease has not been established.

SAMe might interfere with the action of the Parkinson’s drug levodopa.⁶¹ In addition, there may also be risks involved in combining SAMe with standard antidepressants.62 For this reason, you shouldn’t try either combination except under physician supervision.

Interactions You Should Know About

If you are taking:

* Standard antidepressants, including MAO inhibitors, SSRIs, and tricyclics: Do not take SAMe except on a physician’s advice.

* Levodopa for Parkinson’s disease: SAMe might help relieve the side effects of this drug. However, it might also reduce its effectiveness over time.

Click here to review the References for this article at the iHerb Health Library.

If you’d like to see iHerb’s selection of SAM-e products, click here. Use Coupon Code WOW123 to get $5 off any first time order.

5-HTP for Depression, Migraines, Weight Loss and Fibromyalgia Symptoms

Many antidepressant drugs work, at least in part, by raising serotonin levels. The supplement 5-hydroxytryptophan (5-HTP) has been tried in cases of depression for a similar reason: the body uses 5-HTP to make serotonin, so providing the body with 5-HTP might, therefore, raise serotonin levels.

As a supplement, 5-HTP has also been proposed for all the same uses as other antidepressants, including aiding weight loss, preventing migraine headaches, decreasing the discomfort of fibromyalgia, improving sleep quality, and reducing anxiety.

Sources

5-HTP is not found in foods to any appreciable extent. For use as a supplement, it is manufactured from the seeds of an African plant (Griffonia simplicifolia).

Therapeutic Dosages

A typical dosage of 5-HTP is 100 to 300 mg 3 times daily. Once 5-HTP starts to work, it may be possible to reduce the dosage significantly and still maintain good results.

Therapeutic Uses

The primary use of 5-HTP is for depression. Several small short-term studies have found that it may be as effective as standard antidepressant drugs.^1,2 Since standard antidepressants are also used for insomnia and anxiety, 5-HTP has also been suggested as a treatment for those conditions, but there is only very preliminary evidence as yet that it works.³

Similarly, antidepressant drugs are often used for migraine headaches. Some, but not all, studies suggest that regular use of 5-HTP may help reduce the frequency and severity of migraines, as well as help other types of headaches.^4-10 Additionally, preliminary evidence suggests that 5-HTP can reduce symptoms of fibromyalgia¹¹ and perhaps help you lose weight.^12-15

What Is the Scientific Evidence for 5-Hydroxytryptophan?

Depression

• Several small studies have compared 5-HTP to standard antidepressants.¹⁶ The best one was a 6-week study of 63 people given either 5-HTP (100 mg 3 times daily) or an antidepressant in the Prozac family (fluvoxamine, 50 mg 3 times daily).¹⁷ Researchers found equal benefit between the supplement and the drug. However, 5-HTP caused fewer and less severe side effects.

Migraine and Other Headaches

• There is some evidence that 5-HTP may help prevent migraines when taken at a dosage of 400 to 600 mg daily. Lower doses may not be effective.
• In a 6-month trial of 124 people, 5-HTP (600 mg daily) proved equally effective as the standard drug methysergide.¹⁸ The most dramatic benefits observed were reductions in the intensity and duration of migraines. Since methysergide has been proven better than placebo for migraine headaches in earlier studies, the study results provide meaningful, although not airtight, evidence that 5-HTP is also effective.
• Similarly good results were seen in another comparative study, using a different medication and 5-HTP (at a dose of 400 mg daily).¹⁹
• However, in one study, 5-HTP (up to 300 mg daily) was less effective than the drug propranolol.²⁰ Also, in a study involving children, 5-HTP failed to demonstrate benefit.²¹ Other studies that are sometimes quoted as evidence that 5-HTP is effective for migraines actually enrolled adults or children with many different types of headaches (including migraines).^22,23,24
• Putting all this evidence together, it appears likely that 5-HTP can help people with frequent migraine headaches if taken in sufficient doses, but further research needs to be done. In particular, we need a large double-blind study that compares 5-HTP against placebo over a period of several months.
• Finally, an 8-week, double-blind, placebo-controlled trial of 65 individuals (mostly women) with tension headaches found that 5-HTP at a dose of 100 mg 3 times daily did not significantly reduce the number of headaches experienced; however, it did reduce participants’ need to use other pain-relieving medications.²⁵

Obesity (Weight Loss)

• The drug fenfluramine was one member of the now infamous phen-fen treatment for weight loss. Although very successful, fenfluramine was later associated with damage to the valves of the heart and was removed from the market. Because fenfluramine raises serotonin levels, it seems reasonable to believe that other substances that affect serotonin might also be useful for weight reduction.
• Four small double-blind, placebo-controlled clinical trials examined whether 5-HTP can aid weight loss. The first, a double-blind crossover study, found that use of 5-HTP (at a daily dose of 8 mg per kilogram body weight) reduced caloric intake despite the fact that the 19 participants made no conscious effort to eat less.²⁶ Participants given placebo consumed about 2,300 calories per day, while those taking 5-HTP ate only 1,800 calories daily. Use of 5-HTP appeared to lead to a significantly enhanced sense of satiety after eating. Over the course of 5 weeks, women taking 5-HTP effortlessly lost more than 3 lbs.
• A follow-up study by the same research group enrolled 20 overweight women who were trying to lose weight.²⁷ Participants received either 5-HTP (900 mg per day) or placebo for two consecutive 6-week periods. During the first period, there was no dietary restriction, while during the second period participants were encouraged to follow a defined diet expected to lead to weight loss. Participants receiving placebo did not lose weight during either period. However, those receiving 5-HTP lost about 2% of their initial body weight during the no-diet period and an additional 3% while on the diet. Thus, a woman with an initial weight of 170 lbs lost about 3-1/2 lbs after 6 weeks of using 5-HTP without dieting and another 5 lbs while dieting. Once again, participants taking 5-HTP experienced quicker satiety.
• Similar benefits were seen in a double-blind study of 14 overweight women given 900 mg of 5-HTP daily.²⁸
• Finally, a double-blind, placebo-controlled study of 20 overweight individuals with adult-onset diabetes found that use of 5-HTP (750 mg per day) without intentional dieting resulted in about a 4-1/2 lb weight loss over a 2-week period.²⁹ Use of 5-HTP reduced carbohydrate intake by 75% and fat intake to a lesser extent.

Fibromyalgia

• Antidepressants are the primary conventional treatment for fibromyalgia, a little-understood disease characterized by aching, tender muscles, fatigue, and disturbed sleep. One study suggests that 5-HTP may be helpful as well. In this double-blind trial, 50 subjects with fibromyalgia were given either 100 mg of 5-HTP or placebo 3 times daily for a month.³⁰ Those receiving 5-HTP experienced significant improvements in all symptom categories, including pain, stiffness, sleep patterns, anxiety, and fatigue.

Anxiety

• An 8-week, double-blind, placebo-controlled study compared 5-HTP and the drug clomipramine in 45 individuals suffering from anxiety disorders.³¹ The results showed that 5-HTP was effective, but clomipramine was more effective.

Safety Issues

No significant adverse effects have been reported in clinical trials of 5-HTP. Side effects appear to be generally limited to short-term, mild digestive distress and possible allergic reactions.

One potential safety issue with 5-HTP involves an interaction with a medication used for Parkinson’s disease: carbidopa. Several reports suggest that the combination can create skin changes similar to those that occur in the disease scleroderma.^32,33,34

According to several reports, when dogs have consumed excessive amounts of 5-HTP, they developed signs of excess serotonin.³⁹ In humans, this so-called serotonin syndrome includes such symptoms as confusion, agitation, rapid heart rate, high blood pressure, muscle jerks, loss of coordination, sweating, shivering, and fever; rapid breathing, coma, and death are possible. Serotonin syndrome might also occur if 5-HTP is combined with drugs that raise serotonin levels, such as SSRIs (such as, Prozac), other antidepressants, or the pain medication tramadol.

There are some reasons for concern that 5-HTP could increase the risk of “infantile spasms” (technically, massive myoclonic seizure disorder) in developmentally disabled children.^35,40

Although safety in children has not been proven, children have been given 5-HTP in studies without any apparent harmful effects.^36,37,38 Safety in pregnant or nursing women and those with liver or kidney disease has not been established.

Peak X

One report in 1998 raised a potential safety concern with 5-HTP. Researchers discovered evidence of an unidentified substance called peak X in a limited number of 5-HTP products.⁴¹

Peak X has a frightening history involving a supplement related to 5-HTP: tryptophan. The body turns tryptophan into 5-HTP, and the two supplements have similar effects in the body. Until the late 1980s, tryptophan was widely used as a sleep aid. However, it was taken off the market when thousands of people using tryptophan developed a disabling and sometimes fatal blood disorder called eosinophilia myalgia. Peak X, introduced through a manufacturer’s mistake, is thought to have been the cause, although not all experts agree.^42-50

Despite this one report, it seems unlikely that 5-HTP could present the same risk as tryptophan.⁵¹ It is manufactured completely differently; peak X has not been seen again in 5-HTP samples, and no epidemic of eosinophilia myalgia has occurred with 5-HTP use.

Interactions You Should Know About

If you are taking:

• Prescription antidepressants (including SSRIs, MAO inhibitors, or tricyclics), the pain drug tramadol, or migraine drugs in the triptan family (such as sumatriptan): Do not take 5-HTP in addition, except on a physician’s advice.
• The Parkinson’s disease medication carbidopa: Taking 5-HTP at the same time might cause skin changes similar to those that develop in the disease scleroderma.

If you’d like to see iHerb’s selection of 5-HTP products, click here. Use Coupon Code WOW123 to get $5 off any first time order.

Click here to review the References for this article at the iHerb Health Library.