Health for life

Widely available in pharmacies and health stores, phosphatidylserine is a natural food supplement produced from beef, oysters, and soy. Proven to improve cognition and slow memory loss, its a popular treatment for older people experiencing memory impairment. Now a team headed by Prof. Gil Ast and Dr. Ron Bochner of Tel Aviv Universitys Department of Human Molecular Genetics has discovered that the same supplement improves the functioning of genes involved in degenerative brain disorders, including Parkinsons disease and Familial Dysautonomia (FD).

In FD, a rare genetic disorder that impacts the nervous system and appears almost exclusively in the Ashkenazi Jewish population, a genetic mutation prevents the brain from manufacturing healthy IKAP proteins — which likely have a hand in cell migration and aiding connections between nerves — leading to the early degeneration of neurons. When the supplement was applied to cells taken from FD patients, the gene function improved and an elevation in the level of IKAP protein was observed, reports Prof. Ast. These results were replicated in a second experiment which involved administering the supplement orally to mouse populations with FD.

The findings, which have been published in the journal Human Molecular Genetics, are very encouraging, says Prof. Ast. "That we see such an effect on the brain — the most important organ in relation to this disease — shows that the supplement can pass through the blood-brain barrier even when administered orally, and accumulate in sufficient amounts in the brain."

Slowing the death of nerve cells

Already approved for use as a supplement by the FDA, phosphatidylserine contains a molecule essential for transmitting signals between nerve cells in the brain. Prof. Ast and his fellow researchers decided to test whether the same chemical, which is naturally synthesized in the body and known to boost memory capability, could impact the genetic mutation which leads to FD.

Researchers applied a supplement derived from oysters, provided by the Israeli company Enzymotec, to cells collected from FD patients. Noticing a robust effect on the gene, including a jump in the production of healthy IKAP proteins, they then tested the same supplement on mouse models of FD, engineered with the same genetic mutation that causes the disease in humans.

The mice received the supplement orally, every two days for a period of three months. Researchers then conducted extensive genetic testing to assess the results of the treatment. "We found a significant increase of the protein in all the tissues of the body," reports Prof. Ast, including an eight-fold increase in the liver and 1.5-fold increase in the brain. "While the food supplement does not manufacture new nerve cells, it probably delays the death of existing ones," he adds.

Therapeutic potential for Parkinsons

That the supplement is able to improve conditions in the brain, even when given orally, is a significant finding, notes Prof. Ast. Most medications enter the body through the blood stream, but are incapable of breaking through the barrier between the blood and the brain.

In addition, the researchers say the supplements positive effects extend beyond the production of IKAP. Not only did phosphatidylserine impact the gene associated with FD, but it also altered the level of a total of 2400 other genes — hundreds of which have been connected to Parkinsons disease in previous studies.

The researchers believe that the supplement may have a beneficial impact on a number of degenerative diseases of the brain, concludes Prof. Ast, including a major potential for the development of new medications which would help tens of millions of people worldwide suffering from these devastating diseases.

A compound found in broccoli could be key to preventing or slowing the progress of the most common form of arthritis, according to new research led by the University of East Anglia (UEA).

Results from the laboratory study show that sulforaphane slows down the destruction of cartilage in joints associated with painful and often debilitating osteoarthritis. The researchers found that mice fed a diet rich in the compound had significantly less cartilage damage and osteoarthritis than those that were not.

The study, which also examined human cartilage cells and cow cartilage tissue, was funded by medical research charity Arthritis Research UK, the Biotechnology and Biological Sciences Research Councils (BBSRC) Diet and Health Research Industry Club (DRINC) and The Dunhill Medical Trust.

Sulforaphane is released when eating cruciferous vegetables such as Brussels sprouts and cabbage, but particularly broccoli. Previous research has suggested that sulforaphane has anti-cancer and anti-inflammatory properties, but this is the first major study into its effects on joint health.

The researchers discovered that sulforaphane blocks the enzymes that cause joint destruction by stopping a key molecule known to cause inflammation. They wanted to find out if the compound got into joints in sufficient amounts to be effective and their findings are published today in the journal Arthritis & Rheumatism.

More than 8.5 million people in the UK have osteoarthritis, a degenerative disease affecting the hands, feet, spine, hips and knees in particular. According to Arthritis Research UK, the annual cost of the condition to the NHS is £5.2 billion. In 2011, more than 77,000 knee and 66,000 hip replacements were carried out due to osteoarthritis -- approximately one every four minutes.

Aging and obesity are the most common contributors to the condition and due to their effects, the number of people in the UK consulting a GP about knee osteoarthritis alone could rise from 4.7 million in 2010 to 8.3 million by 2035. Currently one in five people over the age of 45 has osteoarthritis in their knee. There is no cure or effective treatment for the disease other than pain relief, which is often inadequate, or joint replacement.

The study involved researchers from UEAs schools of Biological Sciences, Pharmacy and Norwich Medical School, along with the University of Oxford and Norfolk and Norwich University Hospital.

Researchers from the School of Biological Sciences and Norwich Medical School are now embarking on a small scale trial in osteoarthritis patients due to have knee replacement surgery, to see if eating broccoli has similar effects on the human joint. If successful, they hope it will lead to funding for a large scale clinical trial to show the effect of broccoli on osteoarthritis, joint function and pain itself.

Ian Clark, professor of musculoskeletal biology at UEA and the lead researcher, said: "The results from this study are very promising. We have shown that this works in the three laboratory models we have tried, in cartilage cells, tissue and mice. We now want to show this works in humans. It would be very powerful if we could.

"As well as treating those who already have the condition, you need to be able to tell healthy people how to protect their joints into the future. There is currently no way in to the disease pharmaceutically and you cannot give healthy people drugs unnecessarily, so this is where diet could be a safe alternative.

"Although surgery is very successful, it is not really an answer. Once you have osteoarthritis, being able to slow its progress and the progression to surgery is really important. Prevention would be perable and changes to lifestyle, like diet, may be the only way to do that."

Prof Clark added: "Osteoarthritis is a major cause of disability. It is a huge health burden but a huge financial burden too, which will get worse in an increasingly aging and obese population such as ours.

"This study is important because it is about how diet might work in osteoarthritis. Once you know that you can look at other dietary compounds which could protect the joint and ultimately you can advise people what they should be eating for joint health. Developing new strategies for combating age-related diseases such as osteoarthritis is vital, both to improve the quality of life for sufferers and to reduce the economic burden on society."

Arthritis Research UKs medical director Prof Alan Silman said: "This is an interesting study with promising results as it suggests that a common vegetable, broccoli, might have health benefits for people with osteoarthritis and even possibly protect people from developing the disease in the first place.

"Until now research has failed to show that food or diet can play any part in reducing the progression of osteoarthritis, so if these findings can be replicated in humans, it would be quite a breakthrough. We know that exercise and keeping to a healthy weight can improve peoples symptoms and reduce the chances of the disease progressing, but this adds another layer in our understanding of how diet could play its part."

For the small scale trial, funded by DRINC, half the 40 patients will be given super broccoli -- bred to be high in sulforaphane -- to eat for two weeks before their operation. Once the surgery has taken place the researchers will look at whether the compound has altered joint metabolism and if it can be detected in the replaced joints.

"Plant sterols are present in various combinations in nuts, seeds and plant oils. As plant sterols are the equivalents of animal cholesterol, they can in principal influence metabolic processes, where cholesterol is involved," explained Marcus Grimm, Head of the Experimental Neurology Laboratory at Saarland University. "Because they also lower cholesterol levels, they are extensively used in the food industry and as dietary supplements."

High cholesterol levels have long been discussed to increase the risk of developing Alzheimers disease. "Studies have already shown that cholesterol promotes the formation of so-called senile plaques," said Grimm. These plaques, which are composed of proteins, particularly beta-amyloid proteins, deposit at nerve cells within the brain and are regarded as one of the main causes of Alzheimers disease.

The research team based at Saarland Universitys medical campus in Homburg collaborated with scientists from Bonn, Finland and the Netherlands to examine how the sterols that we ingest influence the formation of these plaque proteins. It was found that one sterol in particular, stigmasterol, actually inhibited protein formation. Stigmasterol is most readily found in soybean oil.

"Stigmasterol has an effect on a variety of molecular processes: it lowers enzyme activity, it inhibits the formation of proteins implicated in the development of Alzheimers disease, and it alters the structure of the cell membrane," explained Dr Grimm. "Together, these effects synergistically reduce the production of beta-amyloid proteins." The research team has been able to confirm the positive effect of stigmasterol in tests on animals.

Overall, the researchers were able to demonstrate that the various plant sterols influence different cellular mechanisms and theore have to be assessed individually. "Particularly in the case of Alzheimers disease, it seems expedient to focus on the dietary intake of specific plant sterols rather than a mixture of sterols," explained Dr Grimm. In future studies, the research team wants to determine which other cellular processes in the brain are affected by phytosterols.

Research has also indicated that stigmasterol may be useful in prevention of certain cancers, including ovarian, prostate, breast, and colon cancers. Studies have also indicated that a diet high in phytoesterols may inhibit the absorption of cholesterol and lower serum cholesterol levels by competing for intestinal absorption.