Dr. Kim Zarse from Jena University investigates how low-dose lithium exposure may affect

mortality in nematodes.   (Credit: Photo: Jan-Peter Kasper/University Jena)

European Journal of Nutrition, February 21, 2011 —  A regular uptake of the trace element lithium can considerably promote longevity. This is the result of a new study by scientists of Friedrich Schiller University Jena.

Professor Dr. Michael Ristow’s team along with Japanese colleagues from universities in Oita and Hiroshima have demonstrated by two independent approaches that even a low concentration of lithium leads to an increased life expectancy in humans as well as in a model organism, the roundworm Caenorhabditis elegans.

The research team presents its results in the online edition of the scientific publication European Journal of Nutrition.

Lithium is one of many nutritional trace elements and is ingested mainly through vegetables and drinking water. “The scientific community doesn’t know much about the physiological function of lithium,” project manager Ristow says. According to an earlier study from the US, highly concentrated lithium showed to be life-prolonging in C. elegans, the Professor of Nutrition in Jena continues. “The dosage that has been analyzed back then, however, is clearly beyond the physiologically relevant range and may be poisonous for human beings,” explains Ristow. To find out if lithium has a life-prolonging impact at much lower concentrations, the scientists then examined the impact of lithium in a concentration that is regularly found in ordinary tap water.

In a collaborative effort with Japanese colleagues, the Jena scientists analyzed the mortality rate in 18 adjacent Japanese municipalities in relation to the amount of lithium contained in tap water from the respective regions. “We found that the mortality rate was considerably lower in those municipalities with more lithium in the drinking water,” Ristow explains the key finding. In a second experiment, the Jena scientists examined exactly this range of concentration in the model organism C. elegans. The result was confirmed: “The average longevity of the worms is higher after they have been treated with lithium at this dosage,” Ristow says.

Even though the underlying mechanisms still remain to be clarified, the scientists assume that the higher longevity they observed in humans as well as in nematodes C. elegans can be induced by the trace element lithium.

Moreover, the scientists speculate about using low-dose lithium as a potential dietary supplement in the future. “From previous studies we know already that a higher uptake of lithium through drinking water is associated with an improvement of psychological well-being and with decreased suicide rates,” Professor Ristow explains. While low-dose lithium uptake on the basis of the new data is clearly thought to be beneficial, more studies will be necessary to thoroughly recommend such a supplementation, the scientists conclude.


Journal Reference:

1.                         Kim Zarse, Takeshi Terao, Jing Tian, Noboru Iwata, Nobuyoshi Ishii, Michael Ristow. Low-dose lithium uptake promotes longevity in humans and metazoans. European Journal of Nutrition, 2011; DOI: 10.1007/s00394-011-0171-x

2.

Friedrich-Schiller-Universitaet Jena (2011, February 18). Fountain of youth from the tap? Environmental lithium uptake promotes longevity, scientists demonstrate.

More About Lithium

WHAT IS LITHIUM?

Lithium is a micromineral or trace element that promotes good mental health.  In this article I discuss the role of lithium in the body in greater detail.

WHEN WAS LITHIUM DISCOVERED?

The first records of lithium date back to 1800 when the Brazilian scientist Jozée Bonifácio de Andrada e Silva discovered the mineral petalite (which contains lithium) in Switzerland.  In 1817 Johan August Arfwedson started to study petalite and realised he could not identify 10% of the mineral.  He concluded that this 10% was a new element which he named lithium.  Arfwedson was unable to isolate lithium but a year later in 1818 both Swedish chemist William Thomas Brand and English chemist Sir Humphry Davy managed to extract it.

HOW DOES YOUR BODY USE LITHIUM?

An average human body contains approximately 7 milligrams (mg) of lithium.  The most well known function of this nutrient is in the treatment of mental disorders such as bipolar disorder.  However, it also has a number of other roles in the body.  The list below outlines the main functions of lithium:
– Assisting in the absorption of vitamin B9 and vitamin B12.
– Assisting in the distribution of iodine throughout the body (which can help treat thyroid diseases).
– Breaking down excess uric acid in the blood and kidneys.
– Controlling and preventing episodes of mania (elevated mood at all times) that occur in people suffering from bipolar disorder.
– Controlling glucose metabolism.
– Enhancing the replication of deoxyribonucleic acid (DNA) (which contains important genetic information that is used in the creation of new cells).
– Increasing the grey matter nerve cells in the brain (which support hearing, memory, muscle control, speech and vision).
– Preventing Alzheimer’s disease and dementia (by reducing brain damage and promoting new neural growth).
– Protecting against the negative effects of mood altering drugs such as alcohol, caffeine, marijuana and tobacco.
– Reducing aggressive, self destructive and violent behaviour (based on a number of different research studies).
– Regulating the production of serotonin (a hormone that regulates mood levels).
– Supporting the transmission of messages over neurons.

HOW MUCH LITHIUM DO YOU NEED?

Currently there is no recommended daily allowance (RDA) for lithium.  The American College of Nutrition have suggested a minimum intake of 1mg per day but research suggests the body may require between 2mg and 3mg of lithium per day.  Most studies suggest people get an average of 2mg of lithium per day from their diet which is adequate for the body’s needs.

WHICH FOODS CONTAIN LITHIUM?

Dairy products are an excellent source of lithium with cheese, eggs and milk all good choices.  Drinking water also contains trace amounts of lithium.  Mineral water from springs can also contain high levels of lithium depending upon their location.  Herbs and vegetables are another excellent source of lithium with peppers and tomatoes being particularly rich foods.

WHAT ARE THE SYMPTOMS OF GETTING TOO MUCH LITHIUM?

Consuming excess levels of lithium can have a number of negative side effects.  There is no specific upper limit for this nutrient but research suggests that consuming 100mg per day or more can have adverse effects.  Doses of 5 grams (g) per day or more can be fatal.

Since most foods only contain trace amounts of lithium it is almost impossible to overdose on this nutrient through your diet.

Journal of Lipid Research — Though it has been prescribed for over 50 years to treat bipolar disorder, there are still many questions regarding exactly how lithium works. However, in a study appearing in this month’s Journal of Lipid Research, researchers have provided solid evidence that lithium reduces brain inflammation by adjusting the metabolism of the health-protective omega-3-fatty acid called DHA.

Inflammation in the brain, like other parts of the body, is an important process to help the brain combat infection or injury. However, excess or unwanted inflammation can damage sensitive brain cells, which can contribute to psychiatric conditions like bipolar disorder or degenerative diseases like Alzheimers.

It’s believed that lithium helps treat bipolar disorder by reducing brain inflammation during the manic phase, thus alleviating some of the symptoms. Exactly how lithium operates, though, has been debated.

Mireille Basselin and colleagues at the National Institute of Aging and University of Colorado, Denver, took a detailed approach to this question by using mass spectrometry analysis to analyze the chemical composition of brain samples of both control and lithium-treated rats stressed by brain inflammation.

They found that in agreement with some other studies, rats given a six-week lithium treatment had reduced levels of arachidonic acid and its products, which can contribute to inflammation.

In addition, they also demonstrated, for the first time, that lithium treatment increased levels of a metabolite called 17-OH-DHA in response to inflammation. 17-OH-DHA is formed from the omega-3 fatty acid DHA (docosahexaenoic acid) and is the precursor to a wide range of anti-inflammatory compounds known as docosanoids. Other anti-inflammatory drugs, like aspirin, are known to also enhance docosanoids in their mode of action.

Basselin and colleagues noted that the concentration of DHA did not increase, which suggests that lithium may increase 17-OH-DHA levels by affecting the enzyme that converts DHA to 17-OH-DHA.

By reducing both pro-inflammatory AA products, and increasing anti-inflammatory DHA products, lithium exerts a double-protective effect which may explain why it works well in bipolar treatment. Now that its mechanism is a little better understood, it may lead to additional uses for this chemical.

Journal Reference:

1. Basselin et al. Lithium modifies brain arachidonic and docosahexaenoic metabolism in rat lipopolysaccharide model of neuroinflammation. The Journal of Lipid Research, 2010; 51 (5): 1049 DOI: 10.1194/jlr.M002469

2. American Society for Biochemistry and Molecular Biology (2010, May 24). Uncovering lithium’s mode of action. ScienceDaily. Retrieved February 21, 2011, from http://www.sciencedaily.com­ /releases/2010/05/100521191440.htm

University of Missouri-Columbia, February 21, 2011  —  Nobody enjoys colonoscopies, including mice. University of Missouri researchers are excited about the potential of using genetic biomarkers to predict colon cancer caused by inflammation. A new method developed at the MU Research Animal Diagnostic Laboratory (RADIL) could eventually lead to a method that might eliminate colonoscopies altogether.

While working to develop novel therapeutics for colon cancer, Craig Franklin, associate professor of veterinary pathobiology in the MU College of Veterinary Medicine; Aaron Ericsson, post-doctoral researcher at MU; Mike Lewis, assistant professor of veterinary medicine and surgery; Matt Myles, assistant professor of veterinary pathobiology and Lillian Maggio-Price, professor of comparative medicine at the University of Washington, found biomarkers in mouse feces that predicted inflammation-associated colon cancer. This is the same type of cancer associated with some common inflammatory bowel diseases such as ulcerative colitis and Crohn’s Disease.

The team found that the bacterium that leads to inflammation-associated colon cancer in mice first results in inflammation that can be detected by screening feces for messenger RNA of genes. Franklin believes this discovery could lead to tests for similar genes that are present in humans with early inflammation associated colon cancer. The study was published recently in Neoplasia.

“The assumption was that the gene expression couldn’t be detected in fecal matter because RNA breaks down very rapidly. Historically, this was something that a lot of scientists, including us, hadn’t considered,” Franklin said. “But technology has evolved, and we now have the means of preserving RNA much better than we did 15 years ago.”

As a laboratory animal veterinarian, Franklin believes this discovery also could decrease the number of animals used in research.

“We’re excited about the potential for application in humans, but this also will decrease animal numbers, which is one of our goals,” Franklin said. “This test determines which mice will get cancer in advance, so we won’t need to have as many animals in an experimental group to achieve statistical significance.”

“There’s also no stress on the animal for us to test their fecal matter,” Ericsson said. “Many people put off colonoscopies longer than they should because of the invasiveness and unpleasant nature of the exam, and it’s not pleasant for mice either. That unpleasantness is negated with this test.”

For this study, the team also used a high-powered MRI machine located in the Department of Veterans Affairs facility located at the Harry S. Truman Memorial Veterans’ Hospital. While effective, this technique was not as sensitive as the fecal biomarkers in predicting cancer, and it requires extensive expertise and very expensive equipment. Franklin credits the success of the project to a multidisciplinary team that included Wade Davis, assistant professor of biostatistics; Lixin Ma, assistant professor of radiology, and a multitude of veterinarians.

“It was a large collaboration, and veterinarians are ideal for collaborative medicine because we know the animal model,” Franklin said. “There are several angles that converge here, and we’re now interested in finding collaborators in human medicine that would like to explore this further. Ultimately, I’d envision panels of tests that predict diseases, with this method in the mix.”

Journal Reference:

1.                         Aaron C Ericsson, Matthew Myles, Wade Davis, Lixin Ma, Michael Lewis, Lillian Maggio-Price, and Craig Franklin. Noninvasive Detection of Inflammation-Associated Colon Cancer in a Mouse Model. Neoplasia, 2010; 12 (12): 1054-1065

2.                         University of Missouri-Columbia (2011, February 17). New testing could replace colonoscopies in the future.

Colonoscopies Miss Many Cancers, Study Finds

The New York Times, by Gina Kolata  —  For years, many doctors and patients thought colonoscopies, the popular screening test for colorectal cancer, were all but infallible. Have a colonoscopy, get any precancerous polyps removed, and you should almost never get colon cancer.

Then, last spring, researchers reported the test may miss a type of polyp, a flat lesion or an indented one that nestles against the colon wall. And now, a Canadian study, published Tuesday in the journal Annals of Internal Medicine, found the test, while still widely recommended, was much less accurate than anyone expected.

In the new study, the test missed just about every cancer in the right side of the colon, where cancers are harder to detect but about 40 percent arise. And it also missed roughly a third of cancers in the left side of the colon.

Instead of preventing 90 percent of cancers, as some doctors have told patients, colonoscopies might actually prevent more like 60 percent to 70 percent.

“This is a really dramatic result,” said Dr. David F. Ransohoff, a gasteroenterologist at the University of North Carolina. “It makes you step back and worry, ‘What do we really know?’ ”

Dr. Ransohoff and other screening experts say patients should continue to have the test, because it is still highly effective. But they also recommend that patients seek the best colonoscopists by, for example, asking pointed questions about how many polyps they find and remove. They also say patients should be scrupulous in the unpleasant bowel cleansing that precedes the test, and promptly report symptoms like bleeding even if they occur soon after a colonoscopy.

The American Cancer Society says that even if the test is less effective than many had believed, it has no plans to change its recommended intervals between screenings — the test still prevents most cancers, but the expense and risk of the test argue against doing it more often.

The cancer society and the Centers for Disease Control and Prevention also are focusing on developing measurements of quality so that doctors who do colonoscopies can assess themselves and improve.

But gastroenterologists say that, if nothing else, the study points up the paucity of evidence for the common suggestion that anyone who had a clean bill of health from a colonoscopy is almost totally protected for at least a decade.

“We have to not overpromise,” said Dr. Ransohoff, who wrote an editorial accompanying the colonoscopy paper. “We need to look at the evidence, and we shouldn’t go beyond it.”

The new study matched each of 10,292 people who died of colon cancer to five people who lived in the same area and were of the same age, sex and socioeconomic status. The researchers asked how many patients and control subjects had had colonoscopies and whether the doctors had removed polyps. Then the researchers compared the groups and asked how much the colon cancer death rate had declined in people who had had the screening test.

The results were “a shock,” said Dr. Nancy N. Baxter, the lead author of the paper and a colorectal surgeon at the University of Toronto. When she saw them, she said, “I asked my analyst to rerun the data.”

Now, researchers say, the challenge is to find out why the test missed so many cancers, in particular, those on the right side of the colon, and whether the problem can be fixed.

About 148,000 people will learn they have colon cancer this year, the American Cancer Society reports, and nearly 50,000 will die of it.

It might be that Canadian doctors were not sufficiently skilled. About a third of the colonoscopies were done by general internists and family practitioners who might not have had the experience to do the test well.

But, said Dr. Douglas K. Rex, director of endoscopy and professor of medicine at Indiana University, that cannot be the entire explanation because at least one study, as yet unpublished, involving California Medi-Cal patients also found the test missed many cancers on the right side of the colon.

That leaves several other possibilities.

Perhaps patients did not sufficiently cleanse their bowels of fecal material, a particular problem for the right side of the colon.

“After the prep has been completed, mucus and intestinal secretions start rolling out of the small intestine and colon,” Dr. Rex explained. The secretions, he added, pour from the base of the appendix into the right side of the colon and are “very sticky” and can obscure polyps.

One solution, supported by six studies, is to be sure there is just a short time between when patients finish taking the strong laxative that cleanses their bowel and the colonoscopy, Dr. Rex said. That usually means taking half of the laxative the night before the screening test and the rest in the morning, something that often is not done, he added, but that he and others recommend.

Cancer may also be different in the right colon, researchers said.

Flat and indented polyps tend to cluster in the right colon. And so do another kind, serrated lesions, which, some studies indicate, might turn into cancer much more quickly than typical polyps.

“It’s possible that we will never get as good a result” in the right colon, said Robert Smith, director of screening for the American Cancer Society.

Still, he said, that does not mean that patients should have more frequent colonoscopies. The tests are “hugely expensive,” he said, and insurers may not pay for more frequent colonoscopies. The test also carries a small risk of perforating the bowel. Even if colonoscopies miss some cancers, colon cancer remains a rare disease and, after a colonoscopy, “the likelihood that you have cancer is very, very low,” Dr. Smith said.

Dr. Harold C. Sox, editor of the Annals of Internal Medicine, is choosing another option. He is having a stool test, the fecal occult blood test, between colonoscopies. It looks for blood in the stool, which can arise from colon cancer.

Dr. Smith does not advocate that strategy, saying that the stool test can have false positives from things like red meat or broccoli that have nothing to do with colon cancer. He worries that frequent stool tests will lead to frequent false alarms and frequent colonoscopies without making much of a dent in the colon cancer death rate.

CT colonoscopies, so-called virtual colonoscopies, are not a solution, some screening experts said.

“The issues are prep quality, flat lesions, serrated lesions and people not being careful enough in the inspection process,” Dr. Rex said. There is no evidence, he added, that a virtual colonoscopy will help with the inspection process. And, he said, “it almost certainly is not as effective a technology as colonoscopy for flat and serrated lesions.”

Instead, patients should be compulsive about their bowel prep and be sure the test is done by one of the best colonoscopists in their area, gastroenterologists said. Doctors should find polyps in at least 25 percent of men and 15 percent of women. They should take at least eight minutes to withdraw an endoscope from the colon. And they should do a high volume of screening. Dr. Smith said a high volume was at least three or four colonoscopies a day.

After the test, patients can ask whether the doctor got to the right side of the colon and how that was documented.

Colon cancer experts said people should realize that even if colonoscopies prevent just 60 percent of colon cancer deaths, that still is a lot. Mammograms, for example, prevent 25 percent of breast cancer deaths, and the PSA test for men has not been shown to prevent prostate cancer deaths.

“If I was to provide one main message, it would be that colonoscopies are the way that colon cancer mortality gets reduced,” Dr. Ransohoff said. “Colonoscopy is a good test, but it isn’t completely effective. And you know what? We ought to be happy with that.”

This is the CASPro blood pressure measurement device. (Credit: University of Leicester)

University of Leicester, February 21, 2011  —  In a scientific breakthrough, a new blood pressure measurement device is set to revolutionise the way patients’ blood pressure is measured. The new approach, invented by scientists at the University of Leicester and in Singapore, has the potential to enable doctors to treat their patients more effectively because it gives a more accurate reading than the current method used. It does this by measuring the pressure close to the heart — the central aortic systolic pressure or CASP.

Blood pressure is currently measured in the arm because it is convenient however this may not always accurately reflect what the pressure is in the larger arteries close to the heart.

The new technology uses a sensor on the wrist to record the pulse wave and then, using computerised mathematical modelling of the pulse wave, scientists are able to accurately read the pressure close to the heart. Patients who have tested the new device found it easier and more comfortable, as it can be worn like a watch.

Being able to measure blood pressure in the aorta which is closer to the heart and brain is important because this is where high blood pressure can cause damage. In addition, the pressure in the aorta can be quite different from that traditionally measured in the arm. The new technology will hopefully lead to better identification of those who will most likely benefit from treatment by identifying those who have a high central aortic systolic pressure value. This will be especially important for younger people in whom the pressure measured in the arm can sometimes be quite exaggerated compared to the pressure in the aorta.

A key question is whether measurement of central aortic pressure will become routine in clinical practice. Professor Williams said: “it is not going to replace what we do overnight but it is a big advance. Further work will define whether such measurements are preferred for everybody or whether there is a more defined role in selective cases to better decide who needs treatment and who doesn’t and whether the treatment is working optimally”

The University’s close collaboration with the Singapore-based medical device company HealthSTATS International (“HealthSTATS”) has led to the development of this world-first technique for more accurate blood pressure measurement.

The research work carried out by the University of Leicester was funded by the Department of Health’s National Institute for Health Research (NIHR). The NIHR has invested £3.4million with a further £2.2million Capital funding from the Department of Health to establish a Biomedical Research Unit at Glenfield Hospital, Leicester, dedicated to translational research in cardiovascular research. The work, led by Professor Bryan Williams, Professor of Medicine at the University of Leicester and consultant physician at University Hospitals of Leicester NHS Trust, has the promise to change the way we measure blood pressure.

Professor Williams, who is based in the University of Leicester’s Department of Cardiovascular Sciences at Glenfield Hospital, said: “I am under no illusion about the magnitude of the change this technique will bring about. It has been a fabulous scientific adventure to get to this point and it will change the way blood pressure has been monitored for more than a century. The beauty of all of this, is that it is difficult to argue against the proposition that the pressure near to your heart and brain is likely to be more relevant to your risk of stroke and heart disease than the pressure in your arm.

“Leicester is one of the UK’s leading centres for cardiovascular research and is founded on the close working relationship between the University and the Hospitals which allows us to translate scientific research into patient care more efficiently. Key to our contribution to this work has been the support from the NIHR without which we would not have been able to contribute to this tremendous advance. The support of the NIHR has been invaluable in backing us to take this project from an idea to the bedside. Critical to the success of this project has been the synergies of combining clinical academic work here with HealthSTATS and their outstanding medical technology platform in Singapore. This has been the game-changer and I really do think this is going to change clinical practice.”

Dr. Choon Meng Ting the Chairman and CEO of HealthSTATS said: “This study has resulted in a very significant translational impact worldwide as it will empower doctors and their patients to monitor their central aortic systolic pressure easily, even in their homes and modify the course of treatment for BP-related ailments. Pharmaceutical companies can also use CASP devices for clinical trials and drug therapy. All these will ultimately bring about more cost savings for patients, reduce the incidences of stroke and heart attacks, and save more lives.”

Health Secretary Andrew Lansley said: “I saw this new technique in action in Leicester when I visited a few months ago. This is a great example of how research breakthroughs and innovation can make a real difference to patients’ lives. We want the NHS to become one of the leading healthcare systems in the world and our financial commitment to the National Institute for Health Research reflects this.

“I believe patients deserve the best treatments available and science research like this helps us move closer to making that happen.”

Professor Dame Sally Davies, Director General of Research and Development and Interim Chief Medical Officer at the Department of Health, said:

“This is fantastic work by Professor Williams and his team and I am delighted to welcome these findings. I am particularly pleased that the clinical research took place at the NIHR Biomedical Research Unit in Leicester. NIHR funding for Biomedical Research Centres and Units across England supports precisely this type of translational research, aimed at pulling-through exciting scientific discoveries into benefits for patients and the NHS by contributing to improved diagnostics and treatments.”

Journal Reference:

1. Bryan Williams, Peter S. Lacy, Peter Yan, Chua-Ngak Hwee, Chen Liang, Choon-Meng Ting. Development and Validation of a Novel Method to Derive Central Aortic Systolic Pressure From the Radial Pressure Waveform Using an N-Point Moving Average Method. Journal of the American College of Cardiology, 2011; 57 (8): 951 DOI: 10.1016/j.jacc.2010.09.054

2. University of Leicester (2011, February 20). Groundbreaking technology will revolutionize blood pressure measurement