More than 371 million people worldwide suffer from diabetes, of whom 90% are affected by lifestyle-related diabetes mellitus type 2 (type 2 diabetes).

In new experiments, researchers from the University of Copenhagen working in collaboration with a research group at the University of Cincinnati, USA, have demonstrated that the amino acid arginine improves glucose metabolism significantly in both lean (insulin-sensitive) and obese (insulin-resistant) mice.

"In fact, the amino acid is just as effective as several well-established drugs for type 2 diabetics," says postdoc Christoffer Clemmensen. He has conducted the new experiments based at Faculty of Health and Medical Sciences, University of Copenhagen. He is currently conducting research at the Institute for Diabetes and Obesity at Helmholtz Zentrum M-nchen, the German Research Centre for Environmental Health in Munich.

To test the effect of the amino acid arginine, researchers subjected lean and obese animal models to a so-called glucose tolerance test, which measures the body's ability to remove glucose from the blood over time.

"We have demonstrated that both lean and fat laboratory mice benefit considerably from arginine supplements. In fact, we improved glucose metabolism by as much as 40% in both groups. We can also see that arginine increases the body's production of glucagon-like peptide-1 (GLP-1), an intestinal hormone which plays an important role in regulating appetite and glucose metabolism, and which is therefore used in numerous drugs for treating type 2 diabetes," says Christoffer Clemmensen, and continues:

"You cannot, of course, cure diabetes by eating unlimited quantities of arginine-rich almonds and hazelnuts. However, our findings indicate that diet-based interventions with arginine-containing foods can have a positive effect on how the body processes the food we eat."


The research findings were recently published in the American scientific journal Endocrinology under the heading Oral l-arginine Stimulates GLP-1 Secretion to Improve Glucose Tolerance in Male Mice.

Hormone plays key role

Researchers have known for many years that the amino acid arginine is important for the body's ability to secrete insulin. However, the latest findings show that it is an indirect process. The process is actually controlled by arginine's ability to secrete the intestinal hormone GLP-1, which subsequently affects insulin secretion.

"Mice without GLP-1 receptors are not affected to the same extent by arginine. There is no perceptible improvement in glucose metabolism or insulin secretion, confirming our hypothesis of a close biological connection between GLP-1 and arginine," says Christoffer Clemmensen, who conducted the biological experiments in the USA using a special animal model where the receptor for GLP-1 is genetically inactivated.

The new findings provide optimism for better and more targeted drugs for treating type 2 diabetes; the outlook is long-term, but promising.

"This exciting result has raised several new questions which we want to investigate. Can other amino acids do what arginine does? Which intestinal mechanisms 'measure' arginine and lead to the release of GLP-1? Finally, there is the more long-term perspective - the question of whether the findings can be transferred from mice to humans and be used to design drugs that will benefit diabetes patients," says Professor Hans Br-uner-Osborne, who is continuing work on the project in the research group at the Department of Drug Design and Pharmacology at the University of Copenhagen.
Source:

University of Copenhagen

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

 Alzheimer's dementia is a devastating disease characterized by loss of normal thought parameters and memory that will strike one in ten over the age of 65 and nearly half by the time they reach 85. These scary statistics mean that virtually everyone will be touched in some way by this insidious illness at some point in their lives. A rapidly growing library of scientific evidence continues to emerge that demonstrates there are a number of lifestyle changes that we can make as young and middle-aged adults that can significantly lower our risk of developing Alzheimer's disease.

Researchers from the Barcelona Biomedical Research Institute in Spain publishing in the journal, Neurobiology of Aging have found that the combination of two neuroprotective therapies, voluntary physical exercise, and the daily intake of melatonin have been shown to have a synergistic effect against brain deterioration in several common variants of Alzheimer's disease.

The study's authors found that regular, voluntary exercise and daily intake of melatonin, both of which are known for the effects they have in regulating circadian rhythm, show a synergistic effect against brain deterioration that leads to the memory-robbing disease in a mouse model predisposed to develop the illness. Lead author, Dr. Coral Sanfeliu commented "For years we have known that the combination of different anti-aging therapies such as physical exercise, a Mediterranean diet, and not smoking adds years to one's life... now it seems that melatonin, the sleep hormone, also has important anti-aging effects."

Physical activity and melatonin dramatically lower the risk of Alzheimer's disease progression

To determine the effect of physical activity and melatonin supplementation on developing Alzheimer's dementia, researchers divided the genetically-predisposed mice into three control groups, and compared them to animals that had no known inclination to develop dementia. The animals were designated to undergo different treatment protocols including exercise by allowing unrestricted use of a running wheel, melatonin supplementation with a dose equivalent to 10 mg per kg of body weight, and a combination of melatonin and voluntary physical exercise.

After a period of six months, the study's authors concluded "The state of the mice undergoing treatment was closer to that of the mice with no mutations than to their own initial pathological state. From this we can say that the disease has significantly regressed." The genetically predisposed mice demonstrated a general improvement in behavior, learning, and memory with the three treatments. It should be noted that mice are commonly used for this type of research as they share similar neurobiology characteristics with humans.

Numerous prior studies have highlighted the importance of supplementation with melatonin (one to five milligrams, 30 minutes before bedtime) to encourage natural sleep rhythms, and to help lower risks from cancer and cardiovascular disease. We can now add the combination of regular physical activity and melatonin supplementation to the growing list of health benefits, as the therapy is shown to provide another potent tool in the battle to prevent Alzheimer's disease.

Sources:

http://www.neurobiologyofaging.org
http://www.sciencedaily.com/releases/2012/09/120926110110.htm
http://www.medicalnewstoday.com/releases/250741.php
http://www.eurekalert.org/pub_releases/2012-09/f-sf-mae092612.php