title: A systematic review to evaluate the effectiveness of carnitine supplementation in improving walking performance among individuals with intermittent claudication.
abstract: OBJECTIVE
  To evaluate the evidence for the use of carnitine supplementation in improving walking performance among individuals with intermittent claudication.
  
  
  METHODS
  Systematic review.
  
  
  METHODS
  An electronic search of the literature was performed using MEDLINE (PubMed), Scopus, Cochrane Central Register of Controlled Trials and The Cochrane Library from inception through to November 2012. Search terms included peripheral arterial disease, intermittent claudication and carnitine. Reference lists of review articles and primary studies were also examined. Full reports of published experimental studies including randomized controlled trials and pre-test/post-test trials were selected for inclusion. A quality assessment was undertaken according to the Jadad scale.
  
  
  RESULTS
  A total of 40 articles were retrieved, of which 23 did not meet the inclusion criteria. The 17 included articles reported on a total of 18 experimental studies of carnitine supplementation (5 pre-test/post-test; 8 parallel RCT; 5 cross-over RCT) for improving walking performance in adults with intermittent claudication. For pre-test/post-test studies, 300-2000 mg propionyl-L-carnitine (PLC) was administered orally or intravenously for a maximum of 90 days (7-42 participants) with statistically significant improvements of between 74 m and 157 m in pain free walking distance and between 71 m and 135 m in maximal walking distance across 3 out of 5 studies. Similarly, PLC (600 mg-3000 mg) was administered orally in 7 out of 8 parallel RCTs (22-485 participants), the longest duration being 12 months. All but one of the smallest trials demonstrated statistically significant improvements in walking performance between 31 and 54 m greater than placebo for pain free walking distance and between 9 and 86 m greater than placebo for maximal walking distance. A double-blind parallel RCT of cilostazol plus 2000 mg oral L-carnitine or placebo for 180 days (145 participants) did not demonstrate any significant improvement in walking performance. Of 5 cross-over RCTs (8-20 participants), 4 demonstrated significant improvements in walking performance following administration of 300-6000 mg L-carnitine or PLC. Compared to placebo, pain free walking distance and maximal walking distance improved by 23-132 m and 104 m respectively following carnitine intervention.
  
  
  CONCLUSIONS
  Most trials demonstrated a small or modest improvement in walking performance with administration of PLC or L-carnitine. These findings were largely independent of level or quality of evidence, while there was some evidence that intravenous administration was more effective than oral administration and those with severe claudication may achieve greater benefits than those with moderate claudication. Routine carnitine supplementation in the form of PLC may therefore be a useful adjunct therapy for management of intermittent claudication. Further research is warranted to determine the optimal form, duration, dose and safety of carnitine supplementation across the spectrum of peripheral arterial disease severity and its effect with concurrent supervised exercise programs and best medical therapy. These studies should be supplemented with cost effectiveness studies to ensure that the return on the investment is acceptable.
authors.affiliation: Department of Vascular Surgery, Flinders University, Australia.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Delaney
authors.forename: J Ian
authors.initials: JI
authors.lastname: Spark
authors.forename: Jolene
authors.initials: J
authors.lastname: Thomas
authors.forename: Yew Toh
authors.initials: YT
authors.lastname: Wong
authors.forename: Lok Tsung
authors.initials: LT
authors.lastname: Chan
authors.forename: Michelle D
authors.initials: MD
authors.lastname: Miller
mesh_terms: D002331:Carnitine / Q000627:therapeutic use*; D006801:Humans; D007383:Intermittent Claudication / Q000188:drug therapy* / Q000503:physiopathology*; D014803:Vitamin B Complex / Q000627:therapeutic use*; D016138:Walking / Q000502:physiology*
chemical_list: D014803:Vitamin B Complex; D002331:Carnitine