New research has shown for the first time that omega-3 in fish oil could "substantially and significantly" reduce the signs and symptoms of osteoarthritis.

According to the University of Bristol study, funded by Arthritis Research UK and published in the journal Osteoarthritis and Cartilage, omega-3-rich diets fed to guinea pigs, which naturally develop osteoarthritis, reduced disease by 50 per cent compared to a standard diet.

The research is a major step forward in showing that omega-3 fatty acids, either sourced from fish oil or flax oil, may help to slow down the progression of osteoarthritis, or even prevent it occurring, confirming anecdotal reports and "old wives' tales" about the benefits of fish oil for joint health.

Lead researcher Dr John Tarlton, from the Matrix Biology Research group at the University of Bristol's School of Veterinary Sciences, said classic early signs of the condition, such as the degradation of collagen in cartilage and the loss of molecules that give it shock-absorbing properties, were both reduced with omega-3.

"Furthermore, there was strong evidence that omega-3 influences the biochemistry of the disease, and therefore not only helps prevent disease, but also slows its progression, potentially controlling established osteoarthritis," he said.

Dr Tarlton added: "The only way of being certain that the effects of omega-3 are as applicable to humans as demonstrated in guinea pigs is to apply omega-3 to humans. However, osteoarthritis in guinea pigs is perhaps the most appropriate model for spontaneous, naturally occurring osteoarthritis, and all of the evidence supports the use of omega-3 in human disease."


Medical research director of Arthritis Research UK, Professor Alan Silman, said: "The possibility that omega-3 fatty acids could prevent osteoarthritis from developing has been a tantalising one. Some limited, previous research in dogs has suggested that we were a long way away from understanding the potential use in humans. However, this current research in guinea pigs is exciting as it brings us closer to understanding how omega-3 might fundamentally interfere with the osteoarthritis process, and that it could potentially be taken as a treatment."

On the back of the results of his study, Dr Tarlton said that following government guidelines on dietary intake of omega-3 fatty acids could be effective in reducing the burden of osteoarthritis. Fish oil is far more effective than the flax oil based supplement, but for vegetarians flax oil remains a viable alternative.

"Most diets in the developed world are lacking in omega-3, with modern diets having up to 30 times too much omega-6 and too little omega-3. Taking omega-3 will help redress this imbalance and may positively contribute to a range of other health problems such as heart disease and colitis."

Further studies are needed to determine the influence of omega-3 fatty acids on established disease in guinea pigs, and to confirm the effects in human osteoarthritis, said Dr Tarlton.
Source:

University of Bristol

A common nutritional supplement may be part of the magic in improving the survival rates of babies born with heart defects, researchers report.

Carnitine, a compound that helps transport fat inside the cell powerhouse where it can be used for energy production, is currently used for purposes ranging from weight loss to chest pain.

New research shows it appears to normalize the blood vessel dysfunction that can accompany congenital heart defects and linger even after corrective surgery, said Dr. Stephen M. Black, cell and molecular physiologist at the Vascular Biology Center at the Medical College of Georgia at Georgia Regents University.

"My hope is this is going to have a major, major impact on survival of babies," Black said. About half the babies born with heart defects have excessive, continuous high pressure on their lungs from misdirected blood flow. Early surgery can prevent full-blown pulmonary vascular disease, but scientists are finding more subtle disruptions in the signaling inside blood vessels walls that can be problematic - even deadly - up to 72 hours after surgery.

The good news is the changes are reversible and that carnitine speeds recovery and can even prevent the damage in a lamb model of these human heart defects, according to studies published in the journal Pediatric Research.

Normally, most blood flow bypasses the lungs in utero when the placenta provides blood and oxygen for the baby. Baby's first breaths naturally expand the lungs and blood vessels, activating a process inside the lining of vessels that enables them to accommodate the initial blood surge, then reduce pressure quickly, dramatically and permanently.

This natural transition doesn't occur when heart defects misdirect blood flow. "It's kind of like a chronic fetal-to-newborn transition," said Black, the study's corresponding author. Lungs get pounded with about three times the normal flow and, even when surgeries are done as early as possible to repair the defect, correct blood flow and protect the lungs, the 20 percent death rates from acute pulmonary hypertension have remained unchanged for a decade. "That's 1 in 5 kid (with this condition)," Black said.


Left unchecked, the barrage thickens blood vessels, making them unresponsive, much like those of an elderly individual who has lived for years with uncontrolled high blood pressure. The comparatively brief periods of pounding these babies experience impairs the ability of the endothelial cells, which line blood vessels, to produce nitric oxide, a major dilator of blood vessels.

The shear force disrupts carnitine homeostasis, weakens the mitochondria (the cell powerhouse) and impairs nitric oxide production. To make bad matters worse, the precursor to nitric oxide instead makes more peroxynitrite, prompting endothelial cells to grow and thickening blood vessels. Black was also corresponding author of a recent study in the Journal of Biological Chemistry that showed peroxynitrite does this by turning on the cell survival protein kinase Akt1.

The new study indicates that even without fixing the heart defect, high daily doses of carnitine in the first four weeks of life can prevent endothelial dysfunction. In fact, the laboratory lambs' ability to make nitric oxide is preserved even without the benefit of heart surgery and the responses to the chemical activity that enables blood vessel dilation is normalized, Black said.
Source:

Medical College of Georgia at Georgia Regents University

Taking enough omega-3 fatty acid supplements to change the balance of oils in the diet could slow a key biological process linked to aging, new research suggests.

The study showed that most overweight but healthy middle-aged and older adults who took omega-3 supplements for four months altered a ratio of their fatty acid consumption in a way that helped preserve tiny segments of DNA in their white blood cells.

These segments, called telomeres, are known to shorten over time in many types of cells as a consequence of aging. In the study, lengthening of telomeres in immune system cells was more prevalent in people who substantially improved the ratio of omega-3s to other fatty acids in their diet.

Omega-3 supplementation also reduced oxidative stress, caused by excessive free radicals in the blood, by about 15 percent compared to effects seen in the placebo group.

"The telomere finding is provocative in that it suggests the possibility that a nutritional supplement might actually make a difference in aging," said Jan Kiecolt-Glaser, professor of psychiatry and psychology at Ohio State and lead author of the study.

In another recent publication from this study, Kiecolt-Glaser and colleagues reported that omega-3 fatty acid supplements lowered inflammation in this same group of adults.

"Inflammation in particular is at the heart of so many health problems. Anything that reduces inflammation has a lot of potentially good spinoffs among older adults," she said.

Study participants took either 2.5 grams or 1.25 grams of active omega-3 polyunsaturated fatty acids, which are considered "good fats" that, when consumed in proper quantities, are associated with a variety of health benefits. Participants on the placebo took pills containing a mix of oils representing a typical American's daily intake.

The researchers say this combination of effects suggests that omega-3 supplements could represent a rare single nutritional intervention that has potential to lower the risk for a host of diseases associated with aging, such as coronary heart disease, Type 2 diabetes, arthritis and Alzheimer's disease.

The study is published online and scheduled for later print publication in the journal Brain, Behavior, and Immunity.

Participants received either the placebo or one of the two different doses of omega-3 fatty acids. The supplements were calibrated to contain a ratio of the two cold-water fish oil fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), of seven to one. Previous research has suggested that EPA has more anti-inflammatory properties than DHA.

In the case of fatty acids, omega-3 supplementation alone doesn't tell the whole story of how this dietary change can affect health, explained Martha Belury, professor of human nutrition at Ohio State and a co-author of the study. Also important is the ratio of omega-6 fatty acids to omega-3 fatty acids that are present in a person's blood.

Omega-6 fatty acids come from vegetable oils, and since the 1960s, research has suggested that these oils, too, can help protect the cardiovascular system. However, the typical American diet tends to be heavy on omega-6 fatty acids and comparatively low in omega-3s that are naturally found in cold-water fish such as salmon and tuna. While the ratio of omega-6 to omega-3 fatty acids averages about 15-to-1, researchers tend to agree that for maximum benefit, this ratio should be lowered to 4-to-1, or even 2-to-1.


The long chains - or bigger molecules - that make up EPA and DHA fatty acids are believed to be the secret to their effectiveness, Belury said.

Both groups of participants who took omega-3 supplements showed, on average, lengthening of telomeres compared to overall telomere effects in the placebo group, but the relationship could have been attributed to chance. However, when the researchers analyzed the participants' omega-6 to omega-3 ratio in relationship to telomere lengthening, a lower ratio was clearly associated with lengthened telomeres.

"The idea we were looking at with the ratio of omega-6 to omega-3 fatty acids was an increase in the denominator to make the ratio smaller. In the United States, we need to focus on the omega-3 part because we don't get enough of those," Belury said.

The researchers also measured levels of compounds called F2-isoprostanes to determine levels of oxidative stress, which is linked to a number of conditions that include heart disease and neurodegenerative disorders. Both omega-3 groups together showed an average overall 15 percent reduction in oxidative stress compared to effects seen in the placebo group.

When the scientists revisited their earlier inflammation findings, they also found that decreases in an inflammatory marker in the blood called interleukin-6 (IL-6) were associated with telomere lengthening. In their earlier paper on omega-3s and inflammation, they reported that omega-3 supplements lowered IL-6 by 10 to 12 percent, depending on the dose. By comparison, those taking a placebo saw an overall 36 percent increase in IL-6 by the end of the study.

"This finding strongly suggests that inflammation is what's driving the changes in the telomeres," Kiecolt-Glaser said.

Telomeres are a hot topic in science, and their tendency to shorten is associated with such age-related problems as heart disease and early mortality. These short fragments of DNA act as caps at the end of chromosomes, and can be likened to the protective plastic at the end of a shoelace.

"If that plastic comes off, the shoelace unravels and it doesn't work anymore," said study co-author Ron Glaser, professor of molecular virology, immunology and medical genetics and director of the Institute for Behavioral Medicine Research (IBMR) at Ohio State. "In the same way, every time a cell divides, it loses a little bit of its DNA at the ends, and over time, that can cause significant problems."

Kiecolt-Glaser noted that this population was disease-free and reported very little stress. The study included 106 adults, average age 51 years, who were either overweight or obese and lived sedentary lives. The researchers excluded people taking medications to control mood, cholesterol and blood pressure as well as vegetarians, patients with diabetes, smokers, those routinely taking fish oil, people who got more than two hours of vigorous exercise each week and those whose body mass index was either below 22.5 or above 40.

"People who are less healthy than this group, and especially those who experience chronic stress, may gain even more benefits from omega-3 supplementation," she said.
Source: Brain, Behavior, and Immunity

Arginine therapy may be a safe and inexpensive treatment for acute pain episodes in patients with sickle cell disease, according to results of a recent clinical study. The study was the first randomized placebo-controlled study to demonstrate benefits of arginine therapy in children with sickle cell disease hospitalized for severe pain.

Sickle cell disease is an inherited condition in which the body makes red blood cells containing abnormal hemoglobin, the protein that carries oxygen from the lungs to other cells in the body. This abnormal hemoglobin (hemoglobin S) causes red blood cells to distort into a sickle, or crescent shape that often blocks blood flow in small blood vessels, leading to pain and organ damage.

An acute deficiency of nitric oxide in sickled red blood cells contributes to the episodes of blocked vessels and pain. Since the amino acid arginine is a building block of nitric oxide, researchers hypothesized that arginine could be a beneficial treatment for pain related to sickle cell disease.

Previous research found that a single dose of arginine given to sickle cell patients with acute pain episodes resulted in a significant dose-dependent increase in plasma nitric oxide.

Building on that knowledge, the current research study was a randomized, double blind clinical trial of 38 children with sickle cell disease hospitalized for 56 episodes of pain. The research team discovered a 54 percent reduction in the use of pain medication and significantly lower pain scores at hospital discharge in those treated with arginine over those receiving placebo.


The results were published in the journal Haematologica. First author was Claudia R. Morris, MD, assistant professor of pediatrics at Emory University School of Medicine. She conducted the study while in her previous position at Children's Hospital and Research Center in Oakland, CA, with senior author Elliott P. Vichinsky, MD.

"Episodes of pain due to vaso-occlusion are the leading cause of hospital admission and emergency room visits and are associated with increased mortality, yet there is no effective therapy targeting the underlying cause," says Morris. "Treatment consists only of symptom relief with pain medicines and hydration. There is an urgent need for new therapies for acute sickle cell pain, and a greater than 50 percent reduction in use of pain medication was a remarkable finding."

The study found no problems with safety in the use of arginine therapy. Although the treatment did not result in a significantly shorter length of stay in the hospital, the researchers believe delivering the study drug as early as possible in the emergency department or clinic may have a greater impact on length of stay, since many patients received their first dose of medication more than 24 hours after presenting at the hospital.

A large, multi-center trial is warranted in order to confirm these observations and test the effects of delivering the therapy sooner, they note in the published paper.
Source:

Emory Health Sciences

A study will be published on March 21, 2009 in World Journal of Gastroenterology addresses the question.

A research group in King Saud University, Kingdom of Saudi Arabia investigated, for the first time, the role of carnitine, a naturally occurring compound that is synthesized mainly in the liver, during the development of hepatocarcinogenesis. Authors of the study reported that carnitine deficiency is a risk factor and should be viewed as a mechanism in hepatic carcinogenesis, and that long-term L-carnitine supplementation prevents the development of liver cancer. Therefore, carnitine supplementation alone or in combination with other natural chemopreventive compounds could be used to prevent, slow or reverse the occurrence of liver cancer.

Chemoprevention is defined as the use of naturally occurring and/or synthetic compounds in cancer therapy in which the occurrence of cancer can be entirely prevented, slowed or reversed. L-carnitine is a naturally occurring compound which is primarily located in mitochondria and possesses potential protective effects against many mitochondrial toxic agents. It is derived from two sources; endogenous synthesis, in the liver and kidney, and from exogenous dietary sources such as red meat and dairy products. L-carnitine is an essential cofactor for the translocation of long chain fatty acids from the cytoplasmic compartment into mitochondria, where beta-oxidation enzymes are located for ATP production. Despite the liver being the main organ responsible for endogenous synthesis of L-carnitine, we were unable to find any studies investigating the role of long-term endogenous carnitine depletion and/or carnitine deficiency during induction of hepatic carcinogenesis.

The research team by Professor Sayed-Ahmed from College of Pharmacy, King Saud University used an experimental model of hepatocarcinogenesis under conditions of carnitine depletion and carnitine supplementation.


In the carnitine-depleted rat model, there were a progressive increase in the activities of liver enzymes as well as massive degenerative changes and evidence of pre-neoplastic lesions in liver tissues including clusters of hepatocytes with atypia and an increased proliferative rate, diffuse bridging fibrosis and nodule formation, bile ducts with marked reactive atypia showing nuclear enlargement, high nuclear/cytoplasmic ratio and prominent nucleoli. Interestingly, L-carnitine supplementation resulted in a complete reversal of the increase in liver enzymes compared to normal values, as well as normal liver histology with unremarkable central vein and no evidence of pre-neoplastic lesions in liver tissues.

Due to the fact that liver cancer is one of the major health problems in the world and a large sector of patients seek medical attention at a relatively late stage which increases the cost of treatment, King Saud University granted Prof. Sayed-Ahmed and his colleagues a research project with the following specific aims: (1) to understand the possible molecular mechanisms whereby carnitine deficiency provokes hepatic carcinogenesis. (2) to understand the relationship between hepatic cancer and its resistance to cancer chemotherapy, and (3) to gain knowledge on the possible mechanisms by which carnitine supplementation alone or in combination with other natural chemopreventive compounds could be used to prevent, slow or reverse the occurrence of liver cancer.
Source:

http://www.wjgnet.com/