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Intermittent Claudication
Uses
Other Proposed Treatments
- Arginine
- Beta-carotene or Vitamin E , or a Combination of the Two
- Policosanol
The arteries supplying the legs with blood may become seriously blocked in advanced stages of
atherosclerosis
(commonly, if somewhat incorrectly, known as hardening of the arteries). This can lead to severe, crampy pain when you walk more than a short distance because the muscles are starved for oxygen. This condition is called intermittent claudication. The intensity of intermittent claudication is often measured in the distance a person can walk without pain.
Conventional treatment for intermittent claudication consists of measures to combat atherosclerosis, the drug Trental (pentoxifylline), and other medications. In advanced cases, surgery to improve blood flow may be necessary.
Principal Proposed Natural Treatments
A number of natural treatments may be helpful for intermittent claudication, but it isn't clear whether it is safe to combine them with the medications that may be prescribed at the same time. Medical supervision is definitely necessary for this serious disease.
Ginkgo
Many, but not all, studies support the effectiveness of ginkgo for intermittent claudication. According to 9
double-blind, placebo-controlled
trials, ginkgo can significantly increase pain-free walking distance,
1,34
presumably by increasing circulation. A second review of 11 randomized trials with 477 patients, also found improved pain-free walking distance with ginkgo compared to placebo, however the improvemed distance is not considered clinically relevant.
37
One study enrolled 111 patients and followed them for 24 weeks.
2
Participants were measured for pain-free walking distance by walking up a 12% slope on a treadmill at 2 miles an hour. At the beginning of treatment, both the placebo and ginkgo (120 mg) groups were able to walk about 350 feet without pain.
At the end of the trial, although both groups had improved (the power of placebo is amazing!), the ginkgo group had improved significantly more, showing about a 40% increase in pain-free walking distance as compared to only a 20% improvement in the placebo group.
Similar improvements were also seen in a double-blind, placebo-controlled trial of 60 individuals who had achieved maximum benefit from physical therapy.
3
Taking a higher dose of ginkgo may provide enhanced benefits in intermittent claudication. A 24-week, double-blind, placebo-controlled study of 74 individuals found that ginkgo at a dose of 240 mg per day was more effective than 120 mg per day.
4
A 2009 review of 11 trials with 477 subjects suggested that those who took ginkgo biloba could walk further than control subjects, but these results are limited by differences among the trials.
36
However, not all studies have been positive. In another randomized trail involving 62 individuals (averaging 70 years of age), 300 mg of ginkgo per day was no better than placebo at improving pain-free walking distance over 4 months of treatment.
35
For more information, including dosage and safety issues, see the full
Ginkgo
article.
L-Carnitine
The vitamin-like substance L-carnitine also appears to be of some benefit in intermittent claudication. Although it does not increase blood flow, carnitine appears to increase walking distance by improving energy utilization in the muscles.
5
A 12-month, double-blind, placebo-controlled trial of 485 individuals with intermittent claudication evaluated the potential benefits of a special form of carnitine called propionyl-L-carnitine.
6
Participants with relatively severe disease showed a 44% improvement in walking distance as compared to placebo. However, no improvement was seen in those with mild disease. Benefits were seen in most, but not all, other studies using L-carnitine or propionyl-L-carnitine.
7-16
For more information, including dosage and safety issues, see the full
Carnitine
article.
Inositol Hexaniacinate
The supplement inositol hexaniacinate, a special form of vitamin B
3
, appears to be helpful for intermittent claudication. Double-blind studies involving a total of about 400 individuals have found that it can improve walking distance for people with intermittent claudication.
17-20
For example, in one study, 100 individuals were given either placebo or 4 g of inositol hexaniacinate daily.
21
Over a period of 3 months, participants improved significantly in the number of steps they could take on a special device before experiencing excessive pain.
For more information, including dosage and safety issues, see the full
Vitamin B
3
article.
Mesoglycan
Mesoglycan is a substance found in many tissues in the body, including the joints, intestines, and the lining of blood vessels. A 20-week, double-blind, placebo-controlled trial that enrolled 242 individuals evaluated the effects of mesoglycan in intermittent claudication.
28
Significantly more participants in the mesoglycan group responded to treatment (defined as a greater than 50% improvement in walking distance) than in the placebo group.
For more information, including dosage and safety issues, see the full article on
Mesoglycan
.
The supplement
arginine
has been tried for treatment of intermittent claudication. A couple of poorly designed studies had suggested benefit.
29,30
However, the most recent, largest, and best-designed trial not only failed to find arginine effective, the results suggested that arginine can actually
increase
symptoms of intermittent claudication.
32
Various antioxidants have been suggested for the treatment of intermittent claudication. However, a double-blind, placebo-controlled trial of 1,484 individuals with intermittent claudication found no benefit from vitamin E (50 mg daily), beta-carotene (20 mg daily), or a combination of the two.
27
According to a few studies performed in Cuba, the sugarcane-derived substance
policosanol
is helpful for intermittent claudication.
22, 23, 31
Numerous other Cuban studies reported that sugarcane policosanol lowers cholesterol. However, all these studies were performed by a single set of researchers, and they are financially connected to the product. Several independent studies that attempted to replicate the cholesterol related results failed to find benefit. For this reason, all claims associated with policosanol are in doubt.
See the full
Policosanol
article for more information.
One small study found weak preliminary evidence that
lipoic acid
might improve symptoms in intermittent claudication.
33
Herbs and Supplements to Use Only With Caution
Various herbs and supplements may interact adversely with drugs used to treat intermittent claudication. For more information on this potential risk, see the individual drug article in the
Drug Interactions
section of this database.
References
1
Pittler MH, Ernst E. Ginkgo biloba extract for the treatment of intermittent claudication: a meta-analysis of randomized trials. Am J Med. 2000;108:276-281.
Pittler MH, Ernst E. Ginkgo biloba extract for the treatment of intermittent claudication: a meta-analysis of randomized trials. Am J Med. 2000;108:276-281.
2
Peters H, Kieser M, Holscher U. Demonstration of the efficacy of ginkgo biloba special extract EGb 761 on intermittent claudication—a placebo-controlled, double-blind multicenter trial. Vasa. 1998;27:106-110.
Peters H, Kieser M, Holscher U. Demonstration of the efficacy of ginkgo biloba special extract EGb 761 on intermittent claudication—a placebo-controlled, double-blind multicenter trial. Vasa. 1998;27:106-110.
3
Blume J, Kieser M, Holscher U. Placebo-controlled, double-blind study on the effectiveness of ginkgo biloba special extract EGb 761 in trained patients with intermittent claudication [translated from German]. Vasa. 1996;25:265-274.
Blume J, Kieser M, Holscher U. Placebo-controlled, double-blind study on the effectiveness of ginkgo biloba special extract EGb 761 in trained patients with intermittent claudication [translated from German]. Vasa. 1996;25:265-274.
4
Schweizer J, Hatmann C. Comparison of two dosages of Ginkgo biloba extract EGb 761 in patients with peripheral arterial occlusive disease Fontaine's Stage IIb. A randomized, double-blind, multicentric clinical trial. Arzneimittelforschung. 1999;49:900-904.
Schweizer J, Hatmann C. Comparison of two dosages of Ginkgo biloba extract EGb 761 in patients with peripheral arterial occlusive disease Fontaine's Stage IIb. A randomized, double-blind, multicentric clinical trial. Arzneimittelforschung. 1999;49:900-904.
5
Sabba C, Berardi E, Antonica G, et al. Comparison between the effect of L-propionylcarnitine, L-acetylcarnitine and nitroglycerin in chronic peripheral arterial disease: a haemodynamic double blind echo-Doppler study. Eur Heart J. 1994;15:1348-1352.
Sabba C, Berardi E, Antonica G, et al. Comparison between the effect of L-propionylcarnitine, L-acetylcarnitine and nitroglycerin in chronic peripheral arterial disease: a haemodynamic double blind echo-Doppler study. Eur Heart J. 1994;15:1348-1352.
6
Brevetti G, Diehm C, Lambert D. European multicenter study on propionyl-L-carnitine in intermittent claudication. J Am Coll Cardiol. 1999;34:1618-1624.
Brevetti G, Diehm C, Lambert D. European multicenter study on propionyl-L-carnitine in intermittent claudication. J Am Coll Cardiol. 1999;34:1618-1624.
7
Brevetti G, Perna S, Sabba C, et al. Propionyl-L-carnitine in intermittent claudication: double-blind, placebo-controlled, dose titration, multicenter study. J Am Coll Cardiol. 1995;26:1411-1416.
Brevetti G, Perna S, Sabba C, et al. Propionyl-L-carnitine in intermittent claudication: double-blind, placebo-controlled, dose titration, multicenter study. J Am Coll Cardiol. 1995;26:1411-1416.
8
Bolognesi M, Amodio P, Merkel C, et al. Effect of 8-day therapy with propionyl-L-carnitine on muscular and subcutaneous blood flow of the lower limbs in patients with peripheral arterial disease. Clin Physiol. 1995;15:417-423.
Bolognesi M, Amodio P, Merkel C, et al. Effect of 8-day therapy with propionyl-L-carnitine on muscular and subcutaneous blood flow of the lower limbs in patients with peripheral arterial disease. Clin Physiol. 1995;15:417-423.
9
Brevetti G, Perna S, Sabba C, et al. Superiority of L-propionylcarnitine vs L-carnitine in improving walking capacity in patients with peripheral vascular disease: an acute, intravenous, double-blind, cross-over study. Eur Heart J. 1992;13:251-255.
Brevetti G, Perna S, Sabba C, et al. Superiority of L-propionylcarnitine vs L-carnitine in improving walking capacity in patients with peripheral vascular disease: an acute, intravenous, double-blind, cross-over study. Eur Heart J. 1992;13:251-255.
10
Greco AV, Mingrone G, Bianchi M, et al. Effect of propionyl-L-carnitine in the treatment of diabetic angiopathy: controlled double blind trial versus placebo. Drugs Exp Clin Res. 1992;18:69-80.
Greco AV, Mingrone G, Bianchi M, et al. Effect of propionyl-L-carnitine in the treatment of diabetic angiopathy: controlled double blind trial versus placebo. Drugs Exp Clin Res. 1992;18:69-80.
11
Brevetti G, Chiariello M, Ferulano G, et al. Increases in walking distance in patients with peripheral vascular disease treated with L-carnitine: a double-blind, cross-over study. Circulation. 1988;77:767-773.
Brevetti G, Chiariello M, Ferulano G, et al. Increases in walking distance in patients with peripheral vascular disease treated with L-carnitine: a double-blind, cross-over study. Circulation. 1988;77:767-773.
12
Deckert J. Propionyl-L-carnitine for intermittent claudication. J Fam Pract. 1997;44:533-534.
Deckert J. Propionyl-L-carnitine for intermittent claudication. J Fam Pract. 1997;44:533-534.
13
Sabba C, Berardi E, Antonica G, et al. Comparison between the effect of L-propionylcarnitine, L-acetylcarnitine and nitroglycerin in chronic peripheral arterial disease: a haemodynamic double blind echo-Doppler study. Eur Heart J. 1994;15:1348-1352.
Sabba C, Berardi E, Antonica G, et al. Comparison between the effect of L-propionylcarnitine, L-acetylcarnitine and nitroglycerin in chronic peripheral arterial disease: a haemodynamic double blind echo-Doppler study. Eur Heart J. 1994;15:1348-1352.
14
Pepine CJ. The therapeutic potential of carnitine in cardiovascular disorders. Clin Ther. 1991;13:2-21.
Pepine CJ. The therapeutic potential of carnitine in cardiovascular disorders. Clin Ther. 1991;13:2-21.
15
Brevetti G, Attisano T, Perna S, et al. Effect of L-carnitine on the reactive hyperemia in patients affected by peripheral vascular disease: a double-blind, crossover study. Angiology. 1989;40:857-862.
Brevetti G, Attisano T, Perna S, et al. Effect of L-carnitine on the reactive hyperemia in patients affected by peripheral vascular disease: a double-blind, crossover study. Angiology. 1989;40:857-862.
16
Hiatt WR, Regensteiner JG, Creager MA, et al. Propionyl-L-carnitine improves exercise performance and functional status in patients with claudication. Am J Med. 2001;110:616-622.
Hiatt WR, Regensteiner JG, Creager MA, et al. Propionyl-L-carnitine improves exercise performance and functional status in patients with claudication. Am J Med. 2001;110:616-622.
17
O'Hara J, Jolly PN, Nicol CG. The therapeutic efficacy of inositol nicotinate (Hexopal) in intermittent claudication: a controlled trial. Br J Clin Pract. 1988;42:377-383.
O'Hara J, Jolly PN, Nicol CG. The therapeutic efficacy of inositol nicotinate (Hexopal) in intermittent claudication: a controlled trial. Br J Clin Pract. 1988;42:377-383.
18
Kiff RS, Quick CR. Does inositol nicotinate (Hexopal) influence intermittent claudication? A controlled trial. Br J Clin Pract. 1988;42:141-145.
Kiff RS, Quick CR. Does inositol nicotinate (Hexopal) influence intermittent claudication? A controlled trial. Br J Clin Pract. 1988;42:141-145.
19
Head A. Treatment of intermittent claudication with inositol nicotinate. Practitioner. 1986;230:49-54.
Head A. Treatment of intermittent claudication with inositol nicotinate. Practitioner. 1986;230:49-54.
20
Tyson VCH. Treatment of intermittent claudication. Practitioner. 1979;223:121-126.
Tyson VCH. Treatment of intermittent claudication. Practitioner. 1979;223:121-126.
21
O'Hara J, Jolly PN, Nicol CG. The therapeutic efficacy of inositol nicotinate (Hexopal) in intermittent claudication: a controlled trial. Br J Clin Pract. 1988;42:377-383.
O'Hara J, Jolly PN, Nicol CG. The therapeutic efficacy of inositol nicotinate (Hexopal) in intermittent claudication: a controlled trial. Br J Clin Pract. 1988;42:377-383.
22
Castano G, Mas Ferreiro R, Fernandez L, et al. A long-term study of policosanol in the treatment of intermittent claudication. Angiology. 2001;52:115-125.
Castano G, Mas Ferreiro R, Fernandez L, et al. A long-term study of policosanol in the treatment of intermittent claudication. Angiology. 2001;52:115-125.
23
Castano G, Mas R, Roca J, et al. A double-blind, placebo-controlled study of the effects of policosanol in patients with intermittent claudication. Angiology. 1999;50:123-130.
Castano G, Mas R, Roca J, et al. A double-blind, placebo-controlled study of the effects of policosanol in patients with intermittent claudication. Angiology. 1999;50:123-130.
24
Arruzazabala ML, Valdes S, Mas R, et al. Effect of policosanol successive dose increases on platelet aggregation in healthy volunteers. Pharmacol Res. 1996;34:181-185.
Arruzazabala ML, Valdes S, Mas R, et al. Effect of policosanol successive dose increases on platelet aggregation in healthy volunteers. Pharmacol Res. 1996;34:181-185.
25
Arruzazabala ML, Valdes S, Mas R, et al. Comparative study of policosanol, aspirin and the combination therapy policosanol-aspirin on platelet aggregation in healthy volunteers. Pharmacol Res. 1997;36:293-297.
Arruzazabala ML, Valdes S, Mas R, et al. Comparative study of policosanol, aspirin and the combination therapy policosanol-aspirin on platelet aggregation in healthy volunteers. Pharmacol Res. 1997;36:293-297.
26
Maxwell A, Anderson B, Cooke JP. Improvement in walking distance and quality of life in peripheral arterial disease by a nutritional product designed to enhance nitric oxide activity [abstract]. J Am Coll Cardiol. 1999;33(2 suppl A):277A
Maxwell A, Anderson B, Cooke JP. Improvement in walking distance and quality of life in peripheral arterial disease by a nutritional product designed to enhance nitric oxide activity [abstract]. J Am Coll Cardiol. 1999;33(2 suppl A):277A
27
Tornwall ME, Virtamo J, Haukka JK, et al. The effect of alpha-tocopherol and beta-carotene supplementation on symptoms and progression of intermittent claudication in a controlled trial. Atherosclerosis. 1999;147:193-197.
Tornwall ME, Virtamo J, Haukka JK, et al. The effect of alpha-tocopherol and beta-carotene supplementation on symptoms and progression of intermittent claudication in a controlled trial. Atherosclerosis. 1999;147:193-197.
28
Nenci GG, Gresele P, Ferrari G, et al. Treatment of intermittent claudication with mesoglycan--a placebo-controlled, double-blind study. Thromb Haemost. 2001;86:1181-1187.
Nenci GG, Gresele P, Ferrari G, et al. Treatment of intermittent claudication with mesoglycan--a placebo-controlled, double-blind study. Thromb Haemost. 2001;86:1181-1187.
29
Maxwell AJ, Anderson BE, Cooke JP. Nutritional therapy for peripheral arterial disease: a double-blind, placebo-controlled, randomized trial of HeartBar. Vasc Med. 2000;5:11-19.
Maxwell AJ, Anderson BE, Cooke JP. Nutritional therapy for peripheral arterial disease: a double-blind, placebo-controlled, randomized trial of HeartBar. Vasc Med. 2000;5:11-19.
30
Boger RH, Bode-Boger SM, Thiele W, et al. Restoring vascular nitric oxide formation by L-arginine improves the symptoms of intermittent claudication in patients with peripheral arterial occlusive disease. J Am Coll Cardiol. 1998;32:1336-1344.
Boger RH, Bode-Boger SM, Thiele W, et al. Restoring vascular nitric oxide formation by L-arginine improves the symptoms of intermittent claudication in patients with peripheral arterial occlusive disease. J Am Coll Cardiol. 1998;32:1336-1344.
31
Castano G, Mas R, Fernandez L, et al. Effects of policosanol and lovastatin in patients with intermittent claudication: a double-blind comparative pilot study. Angiology. 2003;54:25-38.
Castano G, Mas R, Fernandez L, et al. Effects of policosanol and lovastatin in patients with intermittent claudication: a double-blind comparative pilot study. Angiology. 2003;54:25-38.
32
Wilson AM, Harada R, Nair N, et al. L-arginine supplementation in peripheral arterial disease. No benefit and possible harm. Circulation. 2007 Jun 25. [Epub ahead of print]
Wilson AM, Harada R, Nair N, et al. L-arginine supplementation in peripheral arterial disease. No benefit and possible harm. Circulation. 2007 Jun 25. [Epub ahead of print]
33
Vincent HK, Bourguignon CM, Vincent KR, Taylor AG. Effects of alpha-lipoic acid supplementation in peripheral arterial disease: a pilot study. J Altern Complement Med. 2007;13:577-584.
Vincent HK, Bourguignon CM, Vincent KR, Taylor AG. Effects of alpha-lipoic acid supplementation in peripheral arterial disease: a pilot study. J Altern Complement Med. 2007;13:577-584.
34
Horsch S, Walther C. Ginkgo biloba special extract EGb 761 in the treatment of peripheral arterial occlusive disease (PAOD)—a review based on randomized, controlled studies. Int J Clin Pharmacol Ther. 2004;42:63-72.
Horsch S, Walther C. Ginkgo biloba special extract EGb 761 in the treatment of peripheral arterial occlusive disease (PAOD)—a review based on randomized, controlled studies. Int J Clin Pharmacol Ther. 2004;42:63-72.
35
Gardner CD, Taylor-Piliae RE, Kiazand A, et al. Effect of Ginkgo biloba (EGb 761) on treadmill walking time among adults with peripheral artery disease: a randomized clinical trial. J Cardiopulm Rehabil Prev. 2008;28:258-265.
Gardner CD, Taylor-Piliae RE, Kiazand A, et al. Effect of Ginkgo biloba (EGb 761) on treadmill walking time among adults with peripheral artery disease: a randomized clinical trial. J Cardiopulm Rehabil Prev. 2008;28:258-265.
36
Nicolai S, Kruidenier LM, Bendermacher B, Prins MH, Teijink J. Ginkgo biloba for intermittent claudication. Cochrane Database of Systematic Reviews. 2009;CD006888.
Nicolai S, Kruidenier LM, Bendermacher B, Prins MH, Teijink J. Ginkgo biloba for intermittent claudication. Cochrane Database of Systematic Reviews. 2009;CD006888.
37
Pittler MH, Ernst E. Ginkgo biloba extract for the treatment of intermittent claudication: a meta-analysis of randomized trials. Am J Med. 2000 Mar;108(4):276-281.
Pittler MH, Ernst E. Ginkgo biloba extract for the treatment of intermittent claudication: a meta-analysis of randomized trials. Am J Med. 2000 Mar;108(4):276-281.
