Uncovering lithium's mode of action

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.

Science Centric | 22 May 2010 10:11 GMT

Source: American Society for Biochemistry and Molecular Biology (ASBMB)

Lithium Orotate targets Alzheimer's and other diseases of the brain.

And patients can’t afford to wait for clinical trials.

In 1997 a groundbreaking paper appeared in the Journal of Biological Chemistry, reporting that lithium interferes with a key process in the brain that damages nerve cells in Alzheimer’s disease. The researchers stated that “these findings could be exploited to develop a novel intervention for Alzheimer’s disease”.

More recent studies in cell culture and lab animals have added weight to this prediction and found additional ways in which lithium protects nerve cells and stimulates the repair of damaged nerve tissue. In a 2004 review of the subject, D.M. Chuang of the (U.S.) National Institutes of Health wrote: “The neuroprotective and neurotrophic actions of lithium have profound clinical implications. In addition to its present use in bipolar patients, lithium could be used to treat acute brain injuries such as stroke and chronic progressive neurodegenerative diseases.” Examples of such diseases are Alzheimer’s, Huntington’s, ALS, Parkinson’s, and other, less well-known, conditions.

Lithium salts have been used to treat manic-depression (‘bipolar disorder’) for more than 50 years, and are still considered to be among the best treatments for this ailment. ‘Bipolar’ patients usually use high doses of lithium carbonate (typically above 900 mg/day) and must receive professional guidance and testing for side effects.

At lower doses lithium has been used in recent years as a dietary supplement usually without medical supervision. Lithium Orotate is effective at less than 150 mg/day, with few or no side effects.

Although the lally-gaggers who control the world’s clinical research programs have yet to conduct a clinical trial of lithium as a prevention or treatment for Alzheimer’s or of any other neurodegenerative disorder, we needn’t wait for them to get their act together. Lithium is available as a nutritional supplement (in the U.S. at any rate). It has a very good safety profile at moderate doses – in fact, some evidence suggests that lithium may be an essential trace mineral in the human body.

Several other applications for lithium supplements have come to light recently:

  • protecting the brain from damage by alcohol
  • treating kleptomania
  • preventing symptoms of Fragile X Syndrome
  • a genetic flaw that is known to cause certain forms of autism
  • learning disabilities
  • anxiety disorders
  • mental retardation

LifeLink’s lithium product is the orotate salt of lithium, not the carbonate. This formulation was inspired by the work of Dr. Hans Nieper, the creative German physician, who used lithium orotate to treat:

  • depression
  • headaches
  • migraine
  • epilepsy
  • alcoholism

Nieper considered orotates to be superior to other anions as bioavailability enhancers for minerals like lithium. Furthermore, orotates have other useful properties:

  • protecting the heart from arrhythmias
  • reducing heart-attack damage
  • lowering mental stress
  • eliminating nerve-damaging deposits of lipofuscin and ceroid pigments.