Acetyl-l-carnitine can improve peripheral neuropathy, study shows

Acetyl-l-carnitine (ALCAR) improves the symptoms of peripheral neuropathy and promotes nerve regeneration, according to a British study published in the July 23^rd edition of AIDS.

Distal symmetrical polyneuropathy (DSP), a type of peripheral neuropathy, is a side effect of certain nucleoside analogue reverse transcriptase inhibitors (NRTIs), especially the dideoxynucleotide drugs d4T (stavudine or Zerit), ddC (zalcitabine or Hivid), and ddI (didanosine or Videx). Toxic neuropathy affects 11-66% of patients taking NRTIs. Given the lack of effective therapies for DSP, discontinuation of NRTIs is often necessary to relieve neuropathic pain.

NRTI-associated neuropathy is thought to result from the disruption of mitochondrial DNA synthesis in nerve cells. When this happens, mitochondrial metabolism in the neurones is decreased and the cells’ long peripheral axons die back, leading to reduced innervation (presence of nerve fibres) in the skin and causing pain, tingling, and numbness in the feet and hands.

Noting that ALCAR is vital for normal mitochondrial metabolism and that serum ALCAR levels are decreased in patients with NRTI-associated neuropathy, Dr. Mike Youle, from the Royal Free Centre for HIV Medicine and colleagues conducted a study of the efficacy of ALCAR supplements in improving neuropathic symptoms. Past research has shown that ALCAR promotes the action of nerve growth factor (NGF), stimulates peripheral nerve regeneration, alleviates pain in patients with diabetic neuropathy, and provides short-term relief of NRTI-associated neuropathy symptoms.

The present study included 21 participants with NRTI-associated DSP who received 1500 mg ALCAR twice daily; the trial also included five HIV-negative control subjects without neuropathy. At study entry the median age was 40 years. About 40% had an HIV viral load below 400 copies/mL and the median CD4 count was 286 cells/mm³. Four subjects had asymptomatic HIV disease, eight had symptomatic disease, and eight had frank AIDS. Eight subjects started the study with grade 1 neuropathy (requiring no pain medication), 10 had grade 2 (requiring non-opioid analgesics), and three had grade 3 (requiring opiates).

Skin biopsies were taken from the lower leg before the start of ALCAR therapy and every 6-12 months thereafter (control subjects had only one biopsy). Samples were “immunostained” using various antibodies and examined under a fluorescent microscope to assess the type and quantity (total area) of nerve fibres in the epidermis (outer skin layer), dermis (inner skin layer), and sweat glands.

Subjects were followed for a mean of 14 months (range 5-33 months). In the pre-treatment biopsies, the DSP patients had reduced nerve fibres in the epidermis, the subdermal plexus, and around the sweat glands compared to healthy control subjects. After six months of ALCAR therapy, nerve fibre morphology normalized.

Looking at all nerve fibre types (identified by protein gene product [PGP] antibody staining), epidermis innervation increased by 34% in the DSP patients after six months of ALCAR therapy, and by 101% after 12 months. Dermis innervation increased by 65% after six months, and exceeded that seen in the control subjects by 24 months. Sweat gland innervation increased by 75% after six months and thereafter remained stable (p

Overall, after six months of ALCAR, nerve fibre density in the DSP patients reached the range found in normal skin (92% of the level of epidermis innervation seen in the control subjects, 80% of the dermis innervation, and 69% for sweat glands). After 24 months of ALCAR, improvement continued (epidermis and dermis) or stabilised (sweat glands).

In addition, the grade of neuropathic pain improved in 76% of ALCAR-treated patients and remained unchanged in 19%. Seven patients improved from grade 1 to grade 0 (asymptomatic), four went from grade 2 to grade 0, and one went from grade 3 to grade 0. Those who stopped ALCAR experienced a worsening of neuropathy symptoms. ALCAR was safe and well tolerated in this study, and was not associated with any adverse side effects.

The mechanism by which ALCAR counteracts NRTI toxicity is not known, but it may reduce mitochondrial DNA damage by a direct antioxidant effect, or it may promote the metabolism of fatty acids and glucose. The researchers speculated that ALCAR may offer benefits besides improving peripheral neuropathy, since mitochondrial toxicity also appears to play a role in lipodystrophy syndrome associated with antiretroviral therapy.

“ALCAR treatment improves symptoms [and] causes peripheral nerve regeneration,” the authors concluded. “ALCAR may now offer an effective, pathogenesis-based management approach, allowing patients to remain on NRTI therapy.”