Lithium's Potential Role in Preventing Alzheimer's Disease
Mineral Benefits Other Conditions Besides
Linda Fugate, PhD
Alzheimer's and other neurodegenerative
diseases are characterized by the death of brain cells. A
research team at Wayne State University School of Medicine
recently reported that lithium helps keep brain cells alive, and
that it should be investigated as a potential agent in the
treatment of Alzheimer's. (1-3)
Lithium is a naturally occurring mineral similar to sodium and
potassium. Small amounts are present in most foods. Large
amounts are used in the treatment of manic depression —also
called bipolar disorder. The Wayne State team was studying
lithium's effects on manic depression when they discovered that
this remarkable mineral can protect brain cells from premature
death. In their Oct. 7, 2000 paper, they reported that lithium
may even cause brain cells to regenerate after a loss from
Two proteins are key to lithium's neuroprotective benefits.
Bcl-2 (named for the B-cell lymphoma/ leukemia-2 gene) protects
brain cells from a variety of injuries, including chemical
oxidants and ionizing radiation. Lithium is the first substance
shown to increase the concentrations of Bcl-2 in brain tissue.
On the other hand, a protein you don't want too much of is
glycogen synthase kinase 3b (GSK-3b). GSK-3b appears to
participate in the production of neurofibrillary tangles, which
are a key feature found in Alzheimer's patients. Lithium was
shown to reduce the levels of GSK-3b.
The research results came from three sources: humans, rats, and
brain cell cultures. The patients all suffered from bipolar
disease (manic depression). Magnetic Resonance Imaging (MRI)
scans of the brain were performed before and after four weeks of
lithium treatment. The researchers were surprised to find that
the patients' brain gray matter increased by an average of 3
In an in vitro study, lithium was shown to increase brain cell
survival. When human brain cells were incubated in a lithium
solution and then exposed to two different toxins, the
lithium-treated cells showed up to a 220 percent increase in
survival rate compared to the control groups. (2)
Although there are no published studies on the effect of lithium
on Alzheimer's, the Wayne State team suggests that the
possibility should be studied. An obvious question is whether
manic depressed people who take lithium have a reduced incidence
of Alzheimer's. Data are not yet available, since at least nine
other drugs can be used to treat manic depression. (4) However,
current data show that lithium plays a vital role in maintaining
Benefits of Lithium
Lithium offers both short and long term benefits for the health
of the nervous system. Table 1 summarizes the known effects. Dr.
Robert Lenox, a psychiatric researcher at the University of
Pennsylvania, commented, We are currently still at the stage of
identifying the pieces of the lithium puzzle; within the next 50
years, we will be putting the puzzle together. (5) Additionally,
Prof. Bjorksten demonstrated that lithium was an effective
aluminum chelator and crosslinkage inhibitor. Bjorksten stated
that lithium continues to be the most effective electrolyte for
aluminum detachment. (6)
Lithium in the Diet
There is growing evidence that lithium may be an essential
mineral in the human diet. Animals on low-lithium diets have
shown reproductive problems, shorter life spans, poor lipid
metabolism, and behavioral abnormalities. (7-9) In
epidemiological studies of humans, low levels of lithium in
drinking water have been correlated with a higher incidence of
mental hospital admissions, (10) violent crime, suicide, drug
addiction, (11) and heart disease. (11) Lithium levels in the
scalp hair of violent criminals and heart disease patients have
been found to be lower than those in healthy volunteers. (13)
The amount of lithium in a normal diet varies considerably.
Table 2 shows dietary intakes of lithium reported in the
literature. These values should be considered approximate, since
different researchers give different answers. Some lithium is
present in essentially all foods, with the highest
concentrations reported in eggs and milk. (14) Water can also be
a substantial source. The lithium content of drinking water in
the United States ranges from 0.00001 to 0.170 mg/liter, with an
average of 0.002 mg/liter. (15,16) El Paso, Texas, has one of
the highest concentrations, and is the location most noted as a
high-lithium, low-mental illness site. (10,11) One region of
Northern Chile has 5 mg/liter lithium in the water, which has
been consumed for years without adverse effects reported — and
even water with 6 to 12 mg/liter lithium from an industrial
outflow has not been shown to cause any obvious problems. (23)
Lithium in Medicine and as a Supplement
Lithium got a bad reputation in the 1940s, when lithium chloride
was tried as a salt substitute for patients on low-salt diets.
(Today, potassium chloride is a more accepted salt substitute.)
The amount of lithium used for this application was toxic — and
even fatal, in some cases. Lithium products were removed from
the market, and American doctors rejected the mineral for many
years. In 1949, the Australian physician John Cade reported that
lithium was an effective treatment for manic depression. It was
not until 1970 that the FDA approved its use for medical
treatment in the United States. (19) By 1996, lithium was
included in a list of 18 elements which might be important for
human nutrition.18 In 1998, the U. S. Department of Agriculture
recognized moderate evidence that lithium should be considered
an ultra-trace element with an established, estimated, or
suspected requirement generally indicated by micrograms/day for
There are 13 minerals commonly found in multi-mineral dietary
supplements: calcium, potassium, magnesium, iron, zinc, boron,
copper, manganese, iodine, molybdenum, chromium, selenium, and
vanadium. Other important minerals in the body are phosphorus
and sodium. Daily Values have been established for most of
these. There are several types of Daily Values: Recommended
Dietary Allowances (RDA), Estimated Safe and Adequate Daily
Dietary Intakes (ESADDI), and Dietary Reference Intakes (DRI),
which include several types of nutrient recommendations. (21)
This hodgepodge of dietary advice was created by the Food and
Nutrition Board, a subsidiary of the National Research Council,
which is part of the National Academy of Sciences.
These categories represent different levels of knowledge about
different nutrients. Lithium does not make any of the lists.
However, Forrest Nielsen of the U S Department of Agriculture
suggested that lithium and other trace elements should be
classified as DAMM nutrients, an acronym for Dietary Allowances
of Minuscule Minerals. (18) Actually, lithium is not that
minuscule. It has a low atomic weight, so the milligrams of
lithium in the diet or in the body look deceivingly low. In
terms of atoms, lithium is more abundant in the body than six of
the minerals that are commonly taken in supplements. Table 3
shows the average concentrations of trace minerals in the human
body. (22) The units are atoms per billion atoms. All minerals
in this table except lithium are commonly included in
Lithium, like sodium, occurs naturally in a number of different
salts. Lithium carbonate and lithium citrate are approved as
prescription forms of lithium. The citrate and carbonate salts
are only slightly soluble in water, and are poorly absorbed by
the cells. Another form of lithium — lithium orotate — is a
highly bioavailable form of lithium that is available as an
over-the-counter dietary supplement. (24) Because of its
superior bioavailability, lower doses of lithium orotate than
lithium carbonate (or lithium citrate) may be used to achieve
therapeutic brain lithium concentrations and relatively stable
serum concentrations. (25)
Lithium orotate has also been demonstrated to be of benefit in
the treatment of alcoholics, and proved useful in alleviating
alcohol-related symptoms of liver dysfunction, seizure
disorders, headaches, hyperthyroidism, affective disorders,
Meniere's syndrome, and liver and lung cancers. (25)
Standard lithium orotate dietary supplements provide 5 mg
lithium. This is 1 to 2 percent of the dose provided by
prescription forms of lithium.
Bipolar patients commonly take 200 to 400 mg lithium per day
(this is approximately 1,000 to 2,000 mg lithium carbonate).
(18) Because the blood levels of lithium citrate or lithium
carbonate that have been demonstrated to be therapeutic are only
slightly below the level that has been determined to be toxic,
patients who take these prescription forms of lithium require
regular blood tests to make sure their serum lithium
concentrations stay below the toxic range. Adverse side effects
and the inconvenience of frequent blood tests cause many
patients to discontinue treatment with these prescription drugs.
Lithium orotate is a safe nutritional supplement that may help
to prevent Alzheimer's disease, alcoholism (and related
conditions) and other neurodegenerative conditions. Because of
its superior bioavailability, lower (and safer) doses of lithium
orotate are as effective as the much higher doses found in
source of nutrients and supplements.
did we qualify them ?
1. Gregory J. Moore, Joseph M. Bebchuk, Ian B. Wilds, Guang
Chen, and Husseini K. Manji, Lithium-Induced Increase in Human
Brain Grey Matter, The Lancet, Oct. 7, 2000, vol. 356, pp.
2. Husseini K. Manji, Gregory J. Moore, and Guang Chen, Lithium
Up-Regulates the Cytoprotective Protein Bcl-2 in the CNS in
Vivo: A Role for Neurotrophic and Neuroprotective Effects in
Manic Depressive Illness, Journal of Clinical Psychiatry 2000,
vol. 61, supplement 9, pp. 82-96.
3. Husseini K. Manji, Gregory J. Moore, and Guang Chen, Lithium
at 50: Have the Neuroprotective Effects of This Unique Cation
Been Overlooked? Biological Psychiatry 1999, vol 46, pp.
4. Trevor Silverstone, Is Lithium Still the Maintenance
Treatment of Choice for Bipolar Disorder? CNS Drugs, Aug. 14,
2000, vol. 2, pp.81-94.
5. Robert H. Lenox and Chang-Gyu Hahn, Overview of the Mechanism
of Action of Lithium in the Brain: Fifty-Year Update, Journal of
Clinical Psychiatry 2000, 61, supplement 9, pp. 5-15.
6. Bjorksten, Johan. Pathways to the decisive extension of the
human specific lifespan, J American Geriatrics Soc, 1977 a, 25:
7. M. Anke, W. Arnhold, B. Groppel, and U. Krause, The
Biological Importance of Lithium, In: Lithium in Biology and
Medicine, ed. G. N. Schrauzer and K. F. Klippel, VCH
Verlagsgesellschaft, Weinheim, New York, pp. 147-167, 1991.
8. H. Klemfuss and G. N. Schrauzer, Effects of Nutritional
Lithium Deficiency on Behavior in Rats, Biol. Trace Element Res.
48, 131-139, 1995.
9. A. I. Fleishman, P. H. Lenz, and M. L. Bierenbaum, Effect of
Lithium upon Lipid Metabolism in Rats, Journal of Nutrition,
104, 1242-1254, 1974.
10. E. B. Dawson, The Relationship of Tap Water and
Physiological Levels of Lithium to Mental Hospital Admission and
Homicide in Texas. In: Lithium in Biology and Medicine, ed. G.
N. Schrauzer and K. F. Klippel, VCH Verlagsgesellschaft,
Weinheim, New York, pp. 147-167, 1991.
11. G. N. Schrauzer and K. P. Shrestha, Lithium in Drinking
Water and the Incidences of Crimes, Suicides, and Arrests
Related to Drug Addictions, Biol. Trace Element Res. 25, pp.
12. P. Blachly, Lithium Content of Drinking Water and Ischemic
Heart Disease, New England Journal of Medicine 281, 682, 1969.
13. G. N. Schrauzer, K. P. Shrestha, and M. F. Flores-Arce,
Lithium in Scalp Hair of Adults, Students, and Violent
Criminals, Biol. Trace Element Res. 34, 161-176, 1992.
14. Ulrich Schafer, Essentiality and Toxicity of Lithium, J.
Trace and Microprobe Techniques, 15(3), 341-349, 1997.
15. C. N. Dufor, E. Becker, Public Water Supplies of the 100
Largest Cities in the United States, 1962, Geological Survey
Water-Supply Paper 1812, p. 364, 1962. Quoted in Ref. 15.
16. R. D. Barr and W. B. Clarke, Regulation of Lithium Levels in
Man: Is There Evidence of Biological Essentiality?, Lithium,
1994, vol. 5, pp. 173-180.
17. Eric O. Uthus and Carol D. Seaborn, Deliberations and
Evaluations of the Approaches, Endpoints and Paradigms for
Dietary Recommendations of the Other Trace Elements, J.
Nutrition 126, 2452S – 2495S, 1996.
18. Forrest H. Nielsen, How Should Dietary Guidance Be Given for
Mineral Elements with Beneficial Actions or Suspected of Being
Essential?, J. Nutrition 126, 2377S – 2385S, 1996.
19. James W. Jefferson and John H. Greist, Lithium in
Psychiatry, CNS Drugs 1(6), 448-464, 1994.
20. Forrest H. Nielsen, Ultratrace Elements in Nutrition:
Current Knowledge and Speculation, The Journal of Trace Elements
in Experimental Medicine 11, 251-274, 1998.
21. Carol Ann Rinzler, Nutrition for Dummies, 2nd ed., IDG
22. Mark Winter, University of Sheffield, England,
23. Elisa G. Triffleman and James W. Jefferson, Naturally
Occurring Lithium, In: Lithium and Cell Physiology, ed. R. O.
Bach and V. S. Gallicchio, Springer-Verlag, New York, pp. 16-24,
24. Dean W. and English J., Lithium Orotate: The Unique, Safe
Mineral with Multiple Uses, Vitamin Research News, July, 1999.
25. Kling MA, Manowitz P, Pollack IW. Rat brain and serum
lithium concentrations after acute injections of lithium
carbonate and orotate. J Pharm Pharmacol 1978 Jun;30(6):368-70.
26. Sartori HE., Lithium orotate in the treatment of alcoholism
and related conditions. Alcohol 1986 Mar-Apr;3(2):97-100.
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