Download carnitine deficiency??? - UCSF | Department of Medicine

AW 9/03
CARNITINE DEFICIENCY???
Key Points: Think about offering carnitine supplementation
1.
ESRD (20mg/kg IV after HD): Patients with intradialytic muscle cramps or hypotension, low energy, myopathy,
cardiomyopathy, or anemia unresponsive to standard therapies.
2.
HIV (2-6gms PO/day): Patients refusing HAART, with myopathic symptoms on AZT, or persistent neuropathic
symptoms on HAART.
Carnitine Shuttle: Carnitine is an amino acid that transports fatty acids from the cytosol to the
mitochondrial matrix where fatty acids are oxidized to produce ATP. Hence carnitine deficiency in skeletal
muscle leads to decreased ability to use energy from fatty acids and thus weakness after exercise and
myopathy.1
Genetic enzyme defects (Present in children)
• Primary carnitine deficiency due to metabolism defect –usually affects skeletal and cardiac
muscle and can result in dilated or hypertrophic cardiomyopathy and may respond to carnitine
supplementation
• Fatty acid transport enzyme deficiency, like carnitine acyl transferase, carnitine
palmitoyltransferase (CPT) I and CPT II. No response to carnitine.
• Beta-oxidation enzyme defects. No response to carnitine
Carnitine Deficiency in Chronic Dialysis
A relative carnitine deficiency can occur in dialyzed patients because dialysis removes carnitine
preferentially to its ester, acylcarnitine, particularly in those who do not eat high carnitine sources such as
red meat. Small controlled and uncontrolled trials have shown carnitine supplementation can improve:
• intradialytic muscle cramps and hypotension
• skeletal muscle weakness and/or myopathy
• cardiomyopathy
• anemia of renal failure that is unresponsive to or requires large doses of erythropoietin.
A National Kidney Foundation consensus paper recommends
supplementation in the cases above. Intravenous carnitine
should be given at a dose of 20mg/kg after dialysis. Oral
carnitine in renal failure may result in a toxic metabolite
during GI absorption causing increased uremia.
Carnitine in HIV/AIDS
• AZT myopathy and NRTI neuropathy – result
from mitochondrial DNA toxicity. Patients on AZT
have been found to have low serum carnitine levels in
some studies. Some in vitro evidence shows that
carnitine can improve mDNA toxicity.
•
Effect on CD4 apoptosis and ceramide levels – One
uncontrolled study of 11 patients not on HAART and
without baseline carnitine deficiency from Italy
showed significant CD4 increases and ceramide
decreases after 120 days. Ceramide is a mediator of
apoptosis and has been shown to enhance HIV
replication.2
Sources: Up To Date 2003 Carnitine metabolism in renal disease and metabolism AND Muscle disease in an HIV-infected patient
Patrick L. Nutrients and HIV. Altern Med Rev. 2000;5: 290-305.
1
Champe PC. Biochemistry 1994, p. 182.
2
Moretti S et al. Effect of L-Carnitine on HIV Infection-Associated Apoptosis. Blood. 1998 May 15;91(10):3817-24.