SAMe As It Ever Was?
Neurological symptoms related to HIV infection -- myelopathy (degeneration of the coatings of nerve fibers in the spinal cord), peripheral neuropathy (nerve pain in the hands and feet) and dementia -- are among the most troubling and difficult to handle. Researchers are now beginning to understand the chemical processes involved in these conditions, which may lead to new treatments.
A substance called S-adenosylmethionine (SAMe) is an important ingredient in reactions used to make a substance that holds myelin together. Myelin is the coating on nerve fibers and when it unravels, signals can go awry, causing pain, weakness, and even paralysis in severe cases. Physicians treating people with HIV-related myelopathy note that the condition resembles one found in patients with deficiencies in reactions involving folate and vitamin B-12.
Levels of these vitamins are not significantly reduced in the spinal fluid of people with HIV, so attention turned to another important substance for the reactions, SAMe. Several studies have found that people with HIV have significant deficiencies in SAMe in the central nervous system. One small study found that intravenous administration of SAMe to people with HIV increased central nervous system levels of the substance.
SAMe is somewhat difficult to get across the blood/brain barrier, so either very large oral doses or intravenous administration is needed. However, methionine is made into SAMe by the body and can be taken orally.
A small open label trial at Beth Israel Medical Center suggested that methionine might help improve HIV-related myelopathy. "The results were encouraging enough that we got a grant from NIH to do a larger study," says Dr. Alessandro DiRocco, the study's principal investigator. The preliminary study followed nine pati" who were each given 6 grams a day (3 in the morning, 3 at night) of methionine. Seven of the nine improved during the six month trial. DiRocco's double-blind study is now in its third year, but is still enrolling patients. For further information, contact Sam Chin at (212) 844-8718.
DiRocco says that myelopathy is commonly missed by doctors. "The early symptoms are very vague," he explains. "They include weakness, particularly going up stairs, muscle stiffness, urinary frequency and urgency, and, in men, impotence. Doctors and friends often say, 'Oh, you're just stressed.'" If myelopathy progresses, it can lead to spasticity, incontinence, trouble walking, and even the inability to walk. DiRocco says that such severe symptoms are rare, largely because myelopathy tends to progress slowly. He says some degree of myelopathy is common in HIV infection, however.
If you have these symptoms, it probably wouldn't hurt to try methionine, says DiRocco, but he adds, "Be sure to see a neurologist first."
If the methionine study doesn't pan out, DiRocco plans to test SAMe itself. He doesn't know whether SAMe or methionine is superior but decided to try the cheaper, easier to administer substance first. Side effects linked to methionine include nausea, vomiting, drowsiness and irritability; however, it is usually well-tolerated and in the pilot study, the only significant side effect experienced was short-term gastrointestinal pain. Methionine is not recommended for people with severe liver damage as excesses of methionine can produce excesses of SAMe, which may cause liver dysfunction or make it worse. Excess methionine can also sometimes lead to excess homocysteine, an amino acid which may be linked with heart disease.
SAMe has already shown some value in the treatment of fibromyalgia (non-specific nerve pain) and Alzheimer's disease. In Alzheimer's, as in HIV, lowered levels of SAMe have been found in the central nervous system. Small studies have found modest, but significant, effects. SAMe is also lowered in depression. Interestingly, there have been several European studies, which found that it relieves depression as well as standard antidepressants. Some have also suggested using it to ease opiate withdrawal svmptoms. It is not known whether methionine would also help with these other conditions -- in some cases, SAMe may work while methionine wouldn't because HIV or other conditions might cause problems with the conversion from methionine to SAMe.
Because most peripheral neuropathy related to HIV is caused by the virus itself or by drugs, while myelopathy seems to result from immune processes which try to fight the virus, methionine or SAMe may not be as useful for HIV-related peripheral neuropathy. SAMe may have potential use in fighting liver disease, however. When you get hepatitis (either the viral version or that caused by drug or alcohol misuse), the nastiest symptoms are caused by something called "intrahepatic cholestasis." In English, this means that bile usually released by the liver into the digestive tract doesn't get where it's supposed to go. As a result, urine turns reddish, bowel movements look gray, fat digestion becomes difficult and nausea and vomiting are common.
SAMe is also involved in the synthesis of glutathione, which plays an important role in the workings of the liver. In liver diseases like hepatitis, this pathway is impaired. Some studies have found that administering SAMe either orally or intravenously can increase glutathione production and reduce the symptoms of cholestasis. However, SAMe levels need to be properly balanced -- just as too little can harm the liver, so can too much. The results of DiRocco's methionine study may help provide greater insight into what levels are most useful as well as into any potential harm. SAMe also seems to play a role in male fertility -- it energizes the sperm.
Back to the Notes from the Underground Spring 1999 Contents Page.
This article was provided by PWA Health Group. It is a part of the publication Notes From the Underground.