Carnitine depletion in HIV
Hi, Rosemary.
Yes, I think that is very likely. A few years ago I gave a talk about this hypothesis to a group in which Dr. Ray Stricker was present. Dr. Stricker has considerable experience in treating both Lyme disease and HIV, practicing in San Francisco. Dr. Stricker asked me if this mechanism occurs in HIV infection, and I said that I think it probably does, but probably has not been studied.
I think it still hasn't been studied very much, but please see the abstracts below with regard to the glutathione and methylation aspects in HIV. I don't know if anyone has made the connection between this and the observed low carnitine in HIV infected patients, but it is well known biochemically that carnitine is synthesized in the body by a methylation reaction on the amino acid lysine. Some carnitine also comes in with meat in the diet.
Best regards,
Rich
Neurology. 1995 Sep;45(9):1678-83.
Cerebrospinal fluid S-adenosylmethionine (SAMe) and glutathione concentrations in HIV infection: effect of parenteral treatment with SAMe.
Castagna A, Le Grazie C, Accordini A, Giulidori P, Cavalli G, Bottiglieri T, Lazzarin A.
Department of Infectious Diseases, S. Raffaele Hospital, Milan, Italy.
Abstract
The methylation and transsulfuration pathways are intimately linked and have been implicated in the progression of neurologic damage and immune cell depletion caused by human immunodeficiency virus (HIV) infection. We studied the following metabolites related to these pathways: S-adenosylmethionine (SAMe), homocysteine, cysteine, cysteinyl-glycine, and glutathione (GSH) in blood and CSF of 16 HIV-infected patients with neurologic complications and 20 HIV-negative control patients undergoing lumbar punctures for other medical reasons. We confirmed recent studies of decreased CSF SAMe concentrations in HIV infection and demonstrated that diastereomers of SAMe are present in CSF but not in plasma or erythrocytes from both HIV-infected and HIV-negative patients. In HIV-infected patients, CSF GSH and cysteinyl-glycine, but not homocysteine or cysteine, were significantly reduced. This is the first report of decreased CSF GSH induced by HIV infection. GSH has a regulatory effect on the synthesis of SAMe in hepatic tissue, and the same mechanism may also apply in the CNS. Administration of SAMe-butanedisulphonate, 800 mg/d intravenously for 14 days, was associated with significant increases in CSF SAMe and GSH. These findings have potentially important therapeutic implications for the use of SAMe in protecting against SAMe and GSH deficiency in the CNS of HIV-infected patients.
PMID: 7675226 [PubMed - indexed for MEDLINE]
Neurology. 2002 Mar 12;58(5):730-5.
Abnormal cobalamin-dependent transmethylation in AIDS-associated myelopathy.
Di Rocco A, Bottiglieri T, Werner P, Geraci A, Simpson D, Godbold J, Morgello S.
Department of Neurology, Albert Einstein College of Medicine and Beth Israel Medical Center, New York, NY 10003, USA. adirocco@aecom.yu.edu
Abstract
BACKGROUND: White matter vacuolization of the spinal cord is common in patients with AIDS and may lead to clinical manifestations of myelopathy. The pathogenesis of AIDS-associated myelopathy (AM) is unknown and may be related to metabolic abnormalities rather than to direct HIV infection. The striking pathologic similarity between AM and the vacuolar myelopathy associated with vitamin B(12) deficiency suggests that abnormal metabolism of the B(12)-dependent transmethylation pathway may be important in the pathogenesis of AM. METHODS: The authors compared S-adenosyl-methionine (SAM), methionine, homocysteine, and glutathione in serum and CSF of 15 patients with AM vs. 13 HIV-infected controls without myelopathy (HWM). They also compared the results with a non-HIV--infected reference population (NC). All patients had normal B(12), folate, and methylmalonic acid levels. RESULTS: There was a decrease in CSF SAM in the AM group compared with the HWM group (p < 0.0001) and the NC group (p < 0.0001). CSF SAM in the HWM group was also lower than that in the NC group (p = 0.015). Serum methionine was also reduced in serum of the myelopathic group compared with the NC group (p = 0.006). CONCLUSIONS: AM is associated with an abnormality of the vitamin B(12)-dependent transmethylation pathway.
PMID: 11889235 [PubMed - indexed for MEDLINE]
Hi, Rosemary.
Yes, I think that is very likely. A few years ago I gave a talk about this hypothesis to a group in which Dr. Ray Stricker was present. Dr. Stricker has considerable experience in treating both Lyme disease and HIV, practicing in San Francisco. Dr. Stricker asked me if this mechanism occurs in HIV infection, and I said that I think it probably does, but probably has not been studied.
I think it still hasn't been studied very much, but please see the abstracts below with regard to the glutathione and methylation aspects in HIV. I don't know if anyone has made the connection between this and the observed low carnitine in HIV infected patients, but it is well known biochemically that carnitine is synthesized in the body by a methylation reaction on the amino acid lysine. Some carnitine also comes in with meat in the diet.
Best regards,
Rich
Neurology. 1995 Sep;45(9):1678-83.
Cerebrospinal fluid S-adenosylmethionine (SAMe) and glutathione concentrations in HIV infection: effect of parenteral treatment with SAMe.
Castagna A, Le Grazie C, Accordini A, Giulidori P, Cavalli G, Bottiglieri T, Lazzarin A.
Department of Infectious Diseases, S. Raffaele Hospital, Milan, Italy.
Abstract
The methylation and transsulfuration pathways are intimately linked and have been implicated in the progression of neurologic damage and immune cell depletion caused by human immunodeficiency virus (HIV) infection. We studied the following metabolites related to these pathways: S-adenosylmethionine (SAMe), homocysteine, cysteine, cysteinyl-glycine, and glutathione (GSH) in blood and CSF of 16 HIV-infected patients with neurologic complications and 20 HIV-negative control patients undergoing lumbar punctures for other medical reasons. We confirmed recent studies of decreased CSF SAMe concentrations in HIV infection and demonstrated that diastereomers of SAMe are present in CSF but not in plasma or erythrocytes from both HIV-infected and HIV-negative patients. In HIV-infected patients, CSF GSH and cysteinyl-glycine, but not homocysteine or cysteine, were significantly reduced. This is the first report of decreased CSF GSH induced by HIV infection. GSH has a regulatory effect on the synthesis of SAMe in hepatic tissue, and the same mechanism may also apply in the CNS. Administration of SAMe-butanedisulphonate, 800 mg/d intravenously for 14 days, was associated with significant increases in CSF SAMe and GSH. These findings have potentially important therapeutic implications for the use of SAMe in protecting against SAMe and GSH deficiency in the CNS of HIV-infected patients.
PMID: 7675226 [PubMed - indexed for MEDLINE]
Neurology. 2002 Mar 12;58(5):730-5.
Abnormal cobalamin-dependent transmethylation in AIDS-associated myelopathy.
Di Rocco A, Bottiglieri T, Werner P, Geraci A, Simpson D, Godbold J, Morgello S.
Department of Neurology, Albert Einstein College of Medicine and Beth Israel Medical Center, New York, NY 10003, USA. adirocco@aecom.yu.edu
Abstract
BACKGROUND: White matter vacuolization of the spinal cord is common in patients with AIDS and may lead to clinical manifestations of myelopathy. The pathogenesis of AIDS-associated myelopathy (AM) is unknown and may be related to metabolic abnormalities rather than to direct HIV infection. The striking pathologic similarity between AM and the vacuolar myelopathy associated with vitamin B(12) deficiency suggests that abnormal metabolism of the B(12)-dependent transmethylation pathway may be important in the pathogenesis of AM. METHODS: The authors compared S-adenosyl-methionine (SAM), methionine, homocysteine, and glutathione in serum and CSF of 15 patients with AM vs. 13 HIV-infected controls without myelopathy (HWM). They also compared the results with a non-HIV--infected reference population (NC). All patients had normal B(12), folate, and methylmalonic acid levels. RESULTS: There was a decrease in CSF SAM in the AM group compared with the HWM group (p < 0.0001) and the NC group (p < 0.0001). CSF SAM in the HWM group was also lower than that in the NC group (p = 0.015). Serum methionine was also reduced in serum of the myelopathic group compared with the NC group (p = 0.006). CONCLUSIONS: AM is associated with an abnormality of the vitamin B(12)-dependent transmethylation pathway.
PMID: 11889235 [PubMed - indexed for MEDLINE]
