Lithium

 

By Alice R. Laule, M.D.

 

            The topic for this month comes up as a consequence of some new information I gleaned about the trace mineral lithium. For years, I have recommended a nutritional form of lithium to patients who have problems with mood swings, or difficulty handling certain of life’s stressors, particularly if there is a family history of alcoholism. Apparently part of the genetics of alcoholism has to do with glitches in the lithium pathways in the brain. I have also recommended lithium to people to increase the bone marrow production of white blood cells. I also tried it once to increase bone marrow production of platelets, though I’m not sure it helped. (Sidebar: I have since found out that shark liver oil helps increase platelet production, and have patients in whom it really works!)

            Some of you may be familiar with lithium in the pharmaceutical form that is used to treat bipolar syndrome. The pharmaceutical form is strong, and known for having its effective dose and its toxic dose be very nearly the same. While it is enormously helpful for some people with bipolar disorder, it has given lithium a bad name. It’s side effects are tremor, weight gain, and kidney problems of various sorts. It is helpful to take large doses of flax oil or other omega 3 fatty acid and some vitamin E in the form of mixed tocopherols, which reduces the tremor and makes pharmaceutical lithium more pleasant to use. However, I am NOT primarily talking about pharmaceutical lithium here.

            Lithium is a trace element which has important functions in the brain, including protecting brain cells from various toxins, and reducing the ill effects in particular of an over abundance of certain neuro-excitatory neurotransmitters which are useful in balanced amounts but harmful in large amounts. It is essential for two cell signaling pathways in the brain, cell signaling being the way the brain coordinates its activities.

            The thing that caught my attention about lithium at this time is an article in Dr. David Williams’s newsletter, Alternatives for the Health-Conscious Individual. He reports a just-released scientific study in which ALS (Lou Gehrig’s disease) was treated with a combination of riluzole and moderate doses of lithium carbonate (the pharmaceutical form). The patients on riluzole, the drug of choice for ALS, faired much more poorly than those on riluzole and lithium. In fact, those on the combination had greatly reduced progression of their disease, or stopped progressing altogether. To quote from the newsletter, “In effect, the lithium had practically stopped the progression of ALS in its tracks.” (Proc Natl Acad Sci USA 08;105:2052-2057).

            This is big news, and I have at least one patient with an undiagnosed neuro-muscular disease for whom I hope this will be helpful. In the meantime, it also sent me to the internet to research more about this mineral that I had been recommending in its nutritional form for so many years.

 

What I have found is certainly interesting enough for a newsletter.  Of course, as always there was a lot of biochemical data, as researchers are struggling to figure out why lithium has some beneficial effects for bipolar and other disorders. Lithium’s actions turn out to still be rather mysterious. Lithium is related to sodium and potassium, and will get involved with their exchange at a membrane level. When you start talking about things having an effect on cell membrane transfer of ions, you are talking about potentially profound activity. A medical example of this is the “calcium channel blockers” for blood pressure, heart disease, migraine aura, etc. These drugs interfere with transfer of calcium in and out of cells at the cell membrane level, and therefore have many possible effects in the body. A whole lot of our nervous system function involves the exchange of sodium and potassium, in and out through cellular membranes and along nerve fibers. Lithium interferes with potassium going back into the cell. It could be called a “potassium channel blocker.” In effect, what this does is reduce nerve excitability. Scientifically this would be known as a fall in membrane potential, reduced conductability and excitability. Whether you completely understand the terms or not, you can get the sense of it having a calming, smoothing effect.

            The form of lithium I have recommended is lithium orotate primarily, although nutritional lithium is also available as lithium aspartate or gluconate. I found more information for the orotate form than any other. It has been used quite successfully in a study of alcoholics in a treatment center, in which the success rate in getting off alcohol was greatly enhanced by lithium. Lithium orotate passes the blood brain barrier far better than lithium carbonate, so a smaller dose is able to have a good effect without toxicity. Folic acid enhances the brain’s ability to utilize the protective properties of lithium orotate. A fascinating study actually shows a 3% increase in human grey matter in the brain (the stuff we think with) in just four weeks of use of lithium orotate. No wonder it helps with stress! This increase in grey matter does seem to be associated with actually increases in cognitive function. A study in rats showed that lithium increased their spatial memory (think “maze”) in just 24 hours of use.

            Once it is in the brain, it reduces damage from excesses of neuro-excitatory neurotransmitters, glutamate and NMDA. In certain people under certain chronic stresses, the receptors for glutamate and NMDA increase in number, keeping the brain in a chronically excited state, which ultimately damages brain cells. Lithium helps stop this. It increases a brain protective protein called bc1-2.

            Lithium levels can be tested by hair analysis, and in a large study done in Texas, violent criminals were shown to have less hair lithium by a factor of 400. Hair mineral testing from samples around the world showed a correlation between low lithium levels and rates of mental hospital admission, suicide, homicide, rape, arrests of various sorts, alcoholism and drug use. Particularly violent areas of the world, Serbia for one, were found to have a higher rate of lithium deficiency in the population.

            Another study has looked at levels in drinking water, which tend to be all under 5 mg. of lithium for a day’s intake of water, but there still seems to be a correlation between water level in a given county (this was done in Texas) and suicide rate as well as the arrest rate for violent crimes, theft, and burglary, as well as the arrest rate for drug possession.

            Of special interest to me, lithium protects against the effects of aluminum, which can be a neurotoxin and is associated with Alzheimer’s disease, Parkinson’s, depression, and ALS. Lithium even prevents the formation of the neurofibrillary tangles and amyloid production that is found in Alzheimer’s, so it could be a viable treatment for the disease. Certainly, since lilthium orotate is so safe, it should be considered as part of a preventive regimen for anyone with these diseases in their family history.

            The dose range of lithium orotate for prevention of neurological disease is in the 10-20 mg. range.  The ALS treatment trial was done with the pharmaceutical form, and the dose was 150 mg. of lithium carbonate twice daily. Doses of lithium carbonate for bipolar disorder go

 

much higher, but those doses are not of our concern here. Lithium carbonate 300 mg. contains 30 mg. of elemental lithium. The lithium orotate that I got at the health food store contains 5 mg. per capsule. However, remember as noted above, a much higher percentage of this gets past the blood brain barrier than does lithium carbonate. Drinking water amounts of less than 5 mg. daily seem to still have a beneficial effect as well.

            When dosing people for mood swings and difficulty handling stress associated with life, I will often recommend as much as 40 mg. daily of the lithium orotate. This dose has made life (and marriage) possible for some Viet Nam vets, long distance truck drivers, and men and women facing extremely difficult life situations. I have not yet recommended it for women who are survivors of domestic abuse, or survivors of childhood molestation, but after my research, I think it would be well worth a trial.

            I do suggest omega 3 supplementation, and if it is not contained in the supplement (most fish oil contains some vitamin E in each capsule) then some vitamin E as mixed tocopherols should be added. (See the December 2005 newsletter for information about the mixed tocopherol form of vitamin E.) I would be slow to give very much of this supplement to anyone who is pregnant or nursing, or who has renal failure, or who is sodium depleted. It may also not be appropriate for those with arteriosclerotic cardiovascular disease. These are all contraindications to the pharmaceutical form, lithium carbonate. Since lithium is a trace mineral, essential to the body’s proper function, it may not be necessary to be quite so cautious with the nutritional supplemental form of it — however no one has done the studies, and no one knows how much problem doses over 5 mg. a day could cause.

            Other stray facts I picked up about lithium:  It inhibits Epstein Barr virus (chronic fatigue syndrome), herpes virus types 1 and 2 (cold sores and genital herpes), cytomegalovirus, and adenovirus (common cold). Lithium carbonate has been used to decrease outbreaks of herpes.

            Lithium has been used to reduce fibromyalgia symptoms, and cluster headaches, especially when these symptoms are associated with psychiatric symptoms.

            All in all, it makes lithium a fascinating subject, something worthy of more attention, and hopefully more research in the medical field.

 

Enjoy your summer, and stay healthy.

Alice R. Laule, M.D.

 

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