L-carnitine significantly improves cardiac health in patients after a heart attack, say a multicenter team of investigators in a study published today in Mayo Clinic Proceedings. Their findings, based on analysis of key controlled trials, associate L-carnitine with significant reduction in death from all causes and a highly significant reduction in ventricular arrhythmias and anginal attacks following a heart attack, compared with placebo or control.

Heart disease is the leading cause of death in the United States. Although many of the therapies developed in recent decades have markedly improved life expectancy, adverse cardiovascular events such as ventricular arrhythmias and angina attacks still occur frequently after an acute myocardial infarction (heart attack).

It is known that during ischemic events L-carnitine levels are depleted. Investigators sought to determine the effects of targeting cardiac metabolic pathways using L-carnitine to improve free fatty acid levels and glucose oxidation in these patients. By performing a systematic review and meta-analysis of the available studies published over several decades, they looked at the role of L-carnitine compared with placebo or control in patients experiencing an acute myocardial infarction.

L-carnitine is a trimethylamine which occurs in high amounts in red meat and is found in certain other foods, and is also widely available as an over-the-counter nutritional supplement which is claimed to improve energy, weight loss, and athletic performance. Its potential role in treating heart disease was first reported in the late 1970s.

A comprehensive literature search yielded 153 studies, 13, published from 1989-2007, were deemed eligible. All the trials were comparison trials of L-carnitine compared with placebo or control in the setting of acute myocardial infarction.

This systematic review of the 13 controlled trials in 3,629 patients, involving 250 deaths, 220 cases of new heart failure, and 38 recurrent heart attacks, found that L-carnitine was associated with:

    

There were numerically fewer myocardial reinfarctions and heart failure cases associated with L-carnitine, but this did not reach statistical significance.

First author James J. DiNicolantonio, PharmD, Wegmans Pharmacy, Ithaca, NY, observes, "Although therapies for acute coronary syndrome (ACS), including percutaneous coronary intervention, dual antiplatelet therapy, b-blockers (BBs), statins, angiotensin-converting enzyme inhibitors (ACEIs), omega-3 fatty acids, and cardiac rehabilitation, have markedly improved clinical outcomes, adverse cardiovascular (CV) events still occur too frequently after ACS. One promising therapy for improving cardiac health involves using L-carnitine to improve free fatty acid levels and glucose oxidation."


"The potential mechanisms responsible for the observed beneficial impact of L-carnitine in acute myocardial infarction are likely multifactorial and may, in part, be conferred through the ability of L-carnitine to improve mitochondrial energy metabolism in the heart by facilitating the transport of long-chain fatty acids from the cytosol to the mitochondrial matrix, where b-oxidation occurs, removing toxic fatty acid intermediates, reducing ischemia induced by long-chain fatty acid concentrations, and replenishing depleted carnitine concentrations seen in ischemic, infarcted, and failing myocardium," says DiNicolantonio.

L-carnitine is proven to be safe and is readily available over the counter. The investigators agree that the overall results of this meta-analysis support the potential use of L-carnitine in acute myocardial infarction and possibly in secondary coronary prevention and treatment, including angina. They advocate for a larger randomized, multicenter trial to be performed to confirm these results in the modern era of routine revascularization and other intensive medical therapies following acute myocardial infarction. But, says DiNicolantonio, "L-carnitine therapy can already be considered in selected patients with high-risk or persistent angina after acute myocardial infarction who cannot tolerate treatment with ACE inhibitors or beta blockers, considering its low cost and excellent safety profile."

These findings may seem to contradict those reported in a study published earlier this month in Nature Medicine by Robert A. Koeth and others (Koeth, R. A. et al. Nature Med. http://dx.doi.org/10.1038/nm.3145), which demonstrated that metabolism by intestinal microbiota of dietary L-carnitine produced trimethylamine N-oxide (TMAO) and accelerated atherosclerosis in mice. They also noted that omnivorous human subjects produced more TMAO than did vegans or vegetarians following ingestion of L-carnitine, and suggested a possible direct link between L-carnitine, gut bacteria, TMAO, and atherosclerosis and risk of ischemic heart disease.

"The Nature Medicine paper is of interest," agrees senior investigator Carl J. Lavie, M.D.,FACC,FACP,FCCP, Medical Director of the Cardiac Rehabilitation and Prevention Center at the John Ochsner Heart and Vascular Institute at the University of Queensland School of Medicine in New Orleans, "but the main study reported there was in animals, and unlike our study, lacks hard outcomes." He also notes that "there are various forms of 'carnitine' and our relatively large meta-analysis specifically tested L-carnitine on hard outcomes in humans who had already experienced acute myocardial infarction."
Source:

Elsevier Health Sciences

Journal of Biological Chemistry “Paper of the Week” Provides Insight into Vitamin Production

A Case Western Reserve University School of Medicine study in the November 22 issue of Journal of Biological Chemistry, explains how vitamin A is generated from beta carotene, its dietary precursors. The discovery sheds new light into how beta carotene’s enzymes are utilized differently contributing to the vitamin’s production. This insight will help guide solutions for vitamin A deficiency, a global public health problem affecting more than half of all countries, according to the World Health Organization.

The study, named a Paper of the Week, led by Johannes von Lintig, PhD, associate professor of pharmacology, demonstrates that beta-carotene is converted to Vitamin A and not other metabolites, which some theorized were toxic compounds.

Vitamin A deficiency is especially prevalent in developing countries of Asia, due to largely rice-based diets which lack beta-carotene, a member of the micronutrient carotenoid family. The deficiency mainly affects pregnant women and children and leads to blindness and increases morbidity.

Understanding how vitamin A is produced in the body is essential to effective public health interventions. Efforts are underway by humanitarian groups to supplement young children and fortify foods, for example in the form of “golden rice,” rice genetically modified to contain beta-carotene. The von Lintig Laboratory’s discovery validates the benefits of fortifying foods to combat the worldwide deficiency problem. Some reports indicate the problem exists in areas of the U.S. where access to fresh fruits and vegetables is scarce.


While the benefit of beta-carotene and fellow carotenoids are widely known, how the body metabolizes beta-carotene has remained a matter of debate. The reason for this controversy is the existence of the micronutrient’s two different metabolizing enzymes, BCO1 and BCO2. Some studies have suggested BCO2 metabolizes beta-carotene differently, thereby inhibiting the beneficial effects of Vitamin A.

The research team provided evidence that BCO1 directly converts beta-carotene to vitamin A. However, they discovered the second enzyme, BCO2, is also significant. It helps prepare carotenoids, other than beta-carotene, for vitamin A production. Specifically, BCO2 removes the part of the carotenoid that cannot be utilized for vitamin A production. The remaining portion of the carotenoid is then further processed by BCO1 to generate vitamin A.

“Our study shows that beta-carotene’s second enzyme does not produce a toxic compound, as had been proposed by some researchers. Rather, the enzyme aids in the metabolizing of carotenoids, aside from beta-carotene, to become vitamin A,” said von Lintig and concluded “that beta-carotene is an important and safe precursor for vitamin A in our diet. Our findings also suggest that golden rice plants are likely very safe for consumption.”
Source:

http://casemed.case.edu/

A commonly used supplement is likely to improve outcomes and recovery for individuals who sustain a spinal cord injury (SCI), according to research conducted by University of Kentucky neuroscientists.

Sasha Rabchevsky, associate professor of physiology, Patrick Sullivan, associate professor of anatomy and neurobiology, and Samir Patel, senior research scientist -- all of the UK Spinal Cord and Brain Injury Research Center (SCoBIRC) -- have discovered that in experimental models, severe spinal cord injury can be treated effectively by administering the supplement acetyl-L-carnitine or ALC, a derivative of essential amino acids that can generate metabolic energy, soon after injury.

The researchers previously reported that following spinal cord injury, the mitochondria, or energy-generation components of cells, are overwhelmed by chemical stresses and lose the ability to produce energy in the form of the compound adenosine triphosphate (ATP). This leads to cell death at the injury site and, ultimately, paralysis of the body below the injury level.

Rabchevsky, Sullivan and Patel have recently demonstrated that ALC can preserve the vitality of mitochondria by acting as an alternative biofuel providing energy to cells, thus bypassing damaged mitochondrial enzymes and promoting neuroprotection.

Results soon to be published show that systemic administration of ALC soon after a paralyzing injury promoted the milestone recovery of the ability to walk. Unlike the animal control group given no ALC, which regained only slight hindlimb movements, the group treated with ALC recovered hindlimb movements more quickly and were able to stand on all four limbs and walk a month later. Critically, such remarkable recovery was correlated with significant tissue sparing at the injury site following administration of ALC.

Because ALC can be administered orally, and is well-tolerated at relatively high doses in humans, researchers believe that their discovery may be translated easily to clinical practice as an early intervention for people with traumatic spinal cord injuries.

Initial funding for these studies was provided by the Kentucky Spinal Cord and Head Injury Research Trust (KSCHIRT). Based on their findings, the research team has been awarded additional grant funding from the National Institutes of Health (NIH) and the Craig H. Neilsen Foundation, with the aim of enabling the investigators to study the beneficial effects of combining ALC with an antioxidant agent known as N-acetylcysteine amide (NACA). The results were reported at the recent National Neurotrauma Society Symposium in July 2011, and will be presented again at the Society for Neuroscience meeting in November 2011.

When translated into clinical practice, this research is expected to offer a viable pharmacological option for promoting neuroprotection and maximizing functional recover following traumatic spinal cord injury.
Source:

University of Kentucky