Walk farther, intermittent or not …

Propionyl L-Carnitine for Aching Legs
Prolong peak walking time

By Will Block

I,Claudius, a novel by Robert Graves—was written as an autobiography of the Roman Emperor Claudius. It was produced in 1976 for BBC TV as a popular TV serial. At that time, it was all the rage, and the production won four BAFTA awards in 1977 and three Emmys in 1978.

The Latin verb claudicare meaning “to limp” memorializes the infirmity of Emperor Claudius—for which he was often chided, along with an affliction to stammer and an inclination to drool. Claudius spawned the word claudication, which in medicine means limping or lameness. It is no laughing matter.

Intermittent Claudication

When that condition is due to a walking-related, aching, cramping on-and-off pain caused by insufficient blood flow to the legs, it’s called intermittent claudication. That’s because the pain comes and goes intermittently—it begins after a certain distance but stops when the patient stops and rests. It is a cardinal symptom of peripheral artery disease (PAD).

Risk factors for PAD include smoking, high blood pressure, atherosclerosis, diabetes, high cholesterol, and being older than age 60. Claudication is pain induced by too little blood flow, usually during exercise. The perceived level of pain from claudication can range from mild to extremely severe. Claudication is most common in the calves, but it can also affect the feet, thighs, hips, buttocks, or arms.

Approximately 8.5 million people in the United States have PAD, including 12-20% of individuals older than age 60.

Efficacy Measured by Peak Walking Time

In a recent study, the efficacy of propionyl-L-carnitine (PLC) was tested in patients with intermittent claudication in the Chinese population.1 In this study, 239 patients were randomized to receive PLC 2 g/day orally or a placebo for 4 months.

PLC is an endogenous compound that—along with L-carnitine (LC) and acetyl- L-carnitine (ALC)—forms a component of the endogenous carnitine pool in humans and most, if not all, animal species. PLC has therapeutic potential for the treatment of various cardiovascular disorders, since it plays a key role in transporting fatty acids across the mitochondrial membrane for oxidation and energy production.

PLC selectively enters into the mitochondria with carnitine acyltransferase (CAT), transforms into L-carnitine and propionyl coenzyme A, converts into succinic coenzyme A, and then stimulates the Krebs cycle by producing succinic acid esters. Succinic coenzyme A is used as energy material in the Krebs cycle when oxygen utilization is low.

From Dr. Dean* …
Carnitine for Heart Health and More

Acetyl-L-carnitine (ALC) and propionyl-L-carnitine are natural substances that boost our energy by acting as sources of the amino acid carnitine. Carnitine facilitates the transport of fatty acid molecules across mitochondrial membranes.1 Without these fuel molecules, our mitochondria (the cells’ chemical “powerhouses”) would cease functioning—and so would we. Carnitine levels tend to decline with age, so maintaining a healthy supply is a good idea.

Carnitine is important for heart health. A recent meta-analysis reviewed 13 trials with a total of 3629 participants who had already experienced a heart attack. The review indicated that carnitine is helpful for heart disease.2 The study found that carnitine was associated with significant reduction in death from all causes and a highly significant reduction in ventricular arrhythmias and anginal attacks (chest pain due to ischemia of the heart muscle) following a heart attack, compared with placebo or control. In other words, carnitine is extremely helpful to the heart, so much so that it actually heals it!

Clinical trials have shown that carnitine supplements increase exercise capacity in people with heart disease-related chest pain (angina),3 and people with intermittent claudication (pain with exertion in the legs due to atherosclerosis of the lower extremities) were able to walk farther without pain after treatment with carnitine for six months.4 Moreover, in those with congestive heart failure, carnitine increased exercise capacity, improved heart function, and increased survival times.5 Finally, another trial showed that those who took carnitine after suffering a heart attack had a 90 percent decrease in mortality over the next 12 months, compared with those who did not receive carnitine.6

A recent meta-analysis review, subsuming 13 controlled trials with a total of 3629 participants and published in the journal Mayo Clinic Proceedings, indicates that L-carnitine (hereafter carnitine) is helpful for heart disease.7 This type of review, identifying the common patterns of multiple studies, specifically tested carnitine on hard outcomes in humans who had already experienced a heart attack. The study found that carnitine was associated with significant reduction in death from all causes and a highly significant reduction in ventricular arrhythmias and anginal attacks (chest pain due to ischemia of the heart muscle) following a heart attack, compared with placebo or control. In other words, carnitine is extremely helpful to the heart, so much so that it actually heals it!

Carnitine Can Keep You Alive After a Heart Attack

The Mayo Clinic study provides strong evidence for carnitine’s benefits in heart health and represents the largest, most powerful scientific review of carnitine’s cardiovascular benefits to date. Its authors found that carnitine supplementation was associated with a 27% reduction in all-cause mortality, a 65% reduction in ventricular arrhythmias, and a 40% reduction in angina symptoms in patients who had experienced a heart attack. These effects were thought to occur through multiple mechanisms, including improved energy metabolism in the mitochondria, decreased ischemia, and enhanced left ventricle function.

ALC also improves memory and other cognitive functions in people with mild cognitive impairment and early Alzheimer’s disease, exerts a neuro­protective effect, thereby inhibiting the peripheral neuropathy that often accompanies diabetes, and helps to prevent age-related glycation, which degrades the proteins in our eyes’ lenses.


* See Ask Dr. Dean: “Is PropeL Good for Your Heart?” in the September 2015 issue.


References

  1. Marcovina SM, Sirtori C, Peracino A, Gheorghiade M, Borum P, Remuzzi G, Ardehali H. Translating the basic knowledge of mitochondrial functions to metabolic therapy: role of L-carnitine. Transl Res. 2013 Feb;161(2):73-84.
  2. Dinicolantonio JJ, Lavie CJ, Fares H, Menezes AR, O’Keefe JH. L-Carnitine in the secondary prevention of cardiovascular disease: systematic review and meta-analysis. Mayo Clin Proc. 2013 Apr 15. doi:pii: S0025-6196(13)00127-4. 10.1016/j.mayocp.2013.02.007.
  3. Cherchi A, Lai C, Angelino F, Trucco G, Caponnetto S, Mereto PE, Rosolen G, Manzoli U, Schiavoni G, Reale A, et al. Effects of L-carnitine on exercise tolerance in chronic stable angina: a multicenter, double-blind, randomized, placebo controlled crossover study. Int J Clin Pharmacol Ther Toxicol. 1985 Oct;23(10):569-72.
  4. Hiatt WR, Regensteiner JG, Creager MA, Hirsch AT, Cooke JP, Olin JW, Gorbunov GN, Isner J, Lukjanov YV, Tsitsiashvili MS, Zabelskaya TF, Amato A. Propionyl-L-carnitine improves exercise performance and functional status in patients with claudication. Am J Med. 2001 Jun 1;110(8):616-22.
  5. Anand I, Chandrashekhan Y, De Giuli F, Pasini E, Mazzoletti A, Confortini R, Ferrari R. Acute and chronic effects of propionyl-L-carnitine on the hemodynamics, exercise capacity, and hormones in patients with congestive heart failure. Cardiovasc Drugs Ther. 1998 Jul;12(3):291-9.
  6. Davini P, Bigalli A, Lamanna F, Boem A. Controlled study on L-carnitine therapeutic efficacy in post-infarction. Drugs Exp Clin Res. 1992;18(8):355-65.
  7. DiNicolantonio JJ, Lavie CJ, Fares H, Menezes AR, O’Keefe JH. L-carnitine in the secondary prevention of cardiovascular disease: systematic review and meta-analysis. Mayo Clin Proc. 2013 Jun;88(6):544-51.

Improving Peak Walking Time

In the study, the primary efficacy endpoint was the improvement of peak walking time (PWT) after treatment over baseline, and the secondary endpoints were the improvement of claudication onset time (CT) and ankle/brachial index (ABI).

In the PLC group—including all patients who met the inclusion/exclusion criteria, completed the trial and follow-up, and took no less than 70% of the trial medication—PWT increased 1.6 ± 1.6 minutes after treatment.

The study showed PLC significantly prolonged the maximum walking time and walking distance of Chinese patients with peripheral arterial disease.

References

  1. Luo T, Li J, Li L, Yang B, Liu C, Zheng Q, Jin B, Chen Z, Li K, Zhang X, Zhang J. A study on the efficacy and safety assessment of propionyl-L-carnitine tablets in treatment of intermittent claudication. Thromb Res. 2013 Oct;132(4):427-32.


Will Block is the publisher and editorial director of Life Enhancement magazine.

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