Bioelectromagnetics 9:387-391 (1988)

Brief Communication

Lithium as a Normal Metabolite: Some Implications for Cyclotron Resonance of Ions in Magnetic Fields Robert F. Smith Behavioral Radiology Laboratories, USVA Medical Center, Kansas City, Missouri

Cyclotron resonance of ions has been proposed as a mechanism by which weak, extremely- low-frequency (ELF) electromagnetic fields can act on biological systems. Critics of a mechanism predicated on resonance of lithium have argued that this element is virtually absent from the internal milieu of mammals and otherwise plays no role in the normal physiological functioning of the organism. Sophisticated techniques of trace-element anal- ysis have recently revealed that lithium is a normal constituent of tissues of assayed mammals, including those of rats and human beings. There is evidence, too, that lithium is an important, biologically-active element. Cyclotron resonance may or may not be a mechanism by which ELF- and static-magnetic fields at low strengths combine to affect the organism, but rejection of this mechanism on the grounds that lithium is absent or is physiologically inadequate is unwarranted. Lithium is normally present and is metaboli- cally active in many tissues, especially those of the of the neuroendocrine system.

Key words: H fields, trace elements, nutrition

Blackman and colleagues reported in 1985 that an efflux of calcium ions from cells of chicken brains was selectively enhanced during in vitro exposures to a time- varying, ELF (15- or 45-Hz) magnetic (H) field that was combined with exposure to a static H field at flux densities near those of the local geomagnetic norm.

To provide a mechanistic explanation for the data of Blackman et al., Liboff [ 1985al proposed that transmembrane movements of ions exposed to a combined, ac- and-dc H field may be influenced by cyclotron resonance. The movement of the ions in such a resonant state would tend to follow a helical course. Therefore, Liboff [ 1985b] also proposed that, because cells have transmembrane channels formed from helical protein structures, the geometry of the channels may facilitate the movement of ions that are in a condition of cyclotron resonance.

Lithium is not the only ionic species that may be excited to a state of cyclotron resonance. Liboff (1985b) has argued that many physiologically important ions may

Received for review December 17, 1987; revision received April 5 , 1988.

Address reprint requests to Robert F. Smith, Behavioral Radiology Laboratories Research Service ( l a ) , USVA Medical Center, Kansas City, Missouri 64128.

0 1988 Alan R. Liss, Inc.

388 Smith

be excited to resonance by a time-varying H field at frequencies between 10 and 100 Hz if also located in a static H field that corresponds to the averaged value of the geomagnetic field (circa 50 pT).

The first reported experiment to provide a formal test of cyclotron resonance in vivo was performed by Thomas et al. [1986]. Timing of a difficult, but well-learned operant response by rats was selectively disrupted when the animals were individually subjected to a horizontal, 60-Hz H field at 50 pT that was combined with a static H field at 26 pT. The H-field exposure corresponded to the condition necessary to produce cyclotron resonance in free, nonhydrated, lithium ions. Constraints on methodology and limitations of the equipment precluded experiments that could test the effect on ions of well-established importance to neural processes (i.e., potassium, sodium, and calcium).

Although studies that are directly confirmatory of the work by Thomas et al., have not been reported, findings similar to theirs have been reported by S.D. Smith and colleagues 119871. These investigators demonstrated that exposure of a marine diatom (Amphora cofleaefomis) to combined, ac-and-dc H field yielded data that comport with cyclotron resonance. That is, the diatom’s mobility varied in conse- quence of the concentration of calcium ions moving across its cell membrane, and the variable of concentration, in turn, reflected the ion’s cyclotron-resonance peaks.

The conclusion by Thomas et al. [1986] that the operant behavior of their rats was altered as a response to cyclotron resonance of lithium ions has been met with skepticism. My colleague, Don Justesen, for example, was strongly inclined to reject the authors’ explanation of their findings. He informed me in a Personal Communi- cation in 1985 that his graduate-school preceptors of nutrition and pharmacology had claimed that lithium is not metabolically important in mammalian physiology and, indeed, may not be a normal constituent of mammalian tissues. Although convinced of the integritity of the behavioral findings of Thomas et al., Justesen believed that their data would find resolution in a different mechanism.

Recent investigations, which have been based on refined methods of trace- element analysis, provide evidence that lithium is an essential trace element in mammalian nutrition. In a review of the scientific literature on lithium metabolism, Mertz [1986] notes that Cade introduced the use of lithium salts in 1949 as a therapeutic agent for the treatment of “psychotic excitement; ” subsequently, LiCl has been found efficacious in relieving symptoms of manic-depressive psychosis. During the ensuing decades it has been widely held that lithium, the twenty-seventh most abundant element in the biosphere [Mertz, 19861, is biologically utile only in a therapeutic regimen and only in very high, near-toxic doses [Gilman et al., 1980, p. 4301.

Lithium has been isolated in normal human beings.in varying quantities in blood, liver, lung, lymph nodes, ovaries, and testes [Hamilton, 19791, and in the milk of lactating human beings [Hurgoiu et al., 19821 and rats [Patt et al., 19781. Lithium has also been observed in the muscle tissue of seven edible species of fish from the northeastern Pacific Ocean [Teeny et al., 19841, and in rabbit fetuses [Palavinskas et al., 19841.

Mertz [1986] reviewed studies that have revealed the presence of lithium in many of the plants consumed by livestock animals and by human beings. The total human intake is not well established, but it has been estimated to range from 100 to 2,000 pg/day. The lithium that is absorbed through the intestine is probably an order

Lithium as a Normal Metabolite 389

of magnitude below that of the dietary intake. Mertz states that the amount available for biological activity (as contrasted with therapeutic activity) averages somewhat less than 10 ng/g of tissue. Although the concentration of lithium in mammalian tissues is small, it needs to be emphasized that disruption of availability or utilization of trace elements can produce profound effects on the organism [cf., Guyton, 1981, p. 913, with Allaway, 1986, pp. 465-4851.

Relatively few studies have been reported about the consequences of dietary restriction of lithium intake but, according to Mertz [1986], adverse sequelae have been observed in goats and rats that were fed lithium-deficient diets. In contrast to female controls that were provided normal intakes of lithium, deprived goats exhibited significant, detrimental differences in gains of body mass, in rates of impregnation, in perinatal mass of concepti, and in span of life.

Rats fed a low-lithium diet (0.005-0.015 ppm) were compared with rats fed a diet supplemented with lithium (0.5 ppm) [Patt et al., 19781. The rats were observed for three generations. Compared with controls, the rats on a low-lithium diet exhibited decreased fertility of females in the second and third generations.

Another study of rats [Burt, 19821, with far less lithium in both the low-lithium diet (0.3 ppb) and the supplemented diet (500 ppb), showed that inadequate lithium resulted in adverse effects on reproductive success, on survival of litters, on size of litters, on average mass of litters, and on survival of pups to day 21.

The results of the dietary studies of the rat may be explained by the observation that many rat tissues have been identified as lithium bearing. Rat tissues that contained lithium are: blood, liver, kidneys, thymus, cerebrum, spleen, heart, adrenals , pitu- itary, thyroid, ovaries, and mammary glands. I think it important to note that in the dietary-deficiency study of the rat by Patt et al., tissues found to be lithium conserving during deficiency were the thymus, brain, adrenals, and pituitary (88-, 80-, 93-, and 100-percent retained, respectively). The study by Burt confirmed the findings of Patt et al., and an additional site of brain tissue found to be lithium conserving was the hippocampus, a structure critical to memory and learning.

Mertz emphasized that the quantitative data on lithium metabolism are sketchy, and that a need exists for additional analyses and for further development and validation of metabolic assays. In a personal communication [March, 19881, Dr. Richard P. Dowdy, Associate Professor of Nutrition at the University of Missouri, Columbia, noted that, although the accuracy of the absolute values obtained in the two rat studies may be challenged, the relative differences and the conclusions are valid. These caveats aside, the previously cited studies indicate that lithium is a critical dietary constituent.

Although Thomas et al, [1986] and Smith et al, [1987] have provided biological evidence in support of cyclotron resonance, even Liboff [ 1985al has suggested limitations that may preclude it as a biological factor. Validation of cyclotron reso- nance of ions at the membrane level remains open as an empirical and mechanistic question. But criticism of this hypothetical construct, if based on the assumed absence of lithium, must yield to the empirical evidence that a) lithium is a normal trace constituent of human tissues; and that b) lithium has been demonstrated to be nutritionally critical in both of the two mammals tested-rats and goats.

The retention of lithium in the neuroendocrine system indicates that if cyclotron resonance of lithium is involved in alteration of membrane function of mammals, the most fruitful areas of investigation, beyond those at the membrane level, would be

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events involved in immune function, in physiological regulation (including stress responses), in circadian rhythms, and in measures of learning and memory.

Lithium may itself provide the key in determining whether it plays a role in bioelectromagnetic interactions in living organisms. It is naturally abundant in the form of two isotopes: Li7 at 92.58% and Li6 at 7.42% [CRC Handbook, 1974, pp. B-249 and E-691. Bowen [ 19561 found that the lighter isotope of lithium is taken up more readily by yeast. He observed in every reported case of biological enrichment of isotopes that the lighter isotope is absorbed or metabolized faster than the heavier isotope. This is of interest because studies of cyclotron resonance involving lithium have been predicated on the mass of the most abundant isotope. From the formula given by Liboff [1985] and the density of the dc H-field (2.71 X lop5 teslas) calculated to produce cyclotron resonance at 60 Hz [Thomas et al., 19861, it can be demonstrated that the lighter and less abundant isotope (Li6) would achieve cyclotron resonance at 69 Hz, and the heavier isotope (Li7) at 59 hz, a sizeable difference in frequencies.

The importance of this difference in predicted resonance frequency (f,s) may well lie in whether it enables experimental resolution of two fundamental, and intertwined, questions: First, does ionic resonance of any form take place in biological systems under exposure to weak magnetic fields? If so, is cyclotron resonance one of the operating species? By maintaining laboratory animals of different groups on diets that have been enriched by or depleted of one or both lithium isotopes, cyclotron resonance as a mechanism could be put directly to experimental test. The behavioral model employed by Thomas et al. [1986] would yield evidence of a bimodal f,. Responding would be improbable in animals with a confirmed lithium deficiency or in those exposed to H-fields that are not harmonically related to the f,s.

ACKNOWLEDGMENT My archival research for this theoretical note was supported by the Research

Service of the U.S. Veteran’s Administration. I thank Don Justesen for noting that the two, common isotopes of lithium have uncommonly differing charge-mass ratios. This observation may prove highly useful in confirming or disconfirming whether cyclotron resonance occurs in living organisms exposed to weak magnetic fields.

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