Effective Mood Stabilization With a Chelated Mineral Supplement:
An Open-Label Trial in Bipolar Disorder

Bonnie J. Kaplan, Ph.D.; J. Steven A. Simpson, Ph.D., M.D.;
Richard C. Ferre, M.D.; Chris P, Gorman, M.D.;
David M. McMullen, M.D.; and Susan G. Crawford, M.Sc.

Background: To determine in open trials the therapeutic benefit of a nutritional supplement for bipolar disorder.

Method: The sample consisted of 11 patients with DSM-IV-diagnosed bipolar disorder aged 19 to 46 years, who were taking a mean of 2.7 psychotropic medications each at study entry. Three additional patients dropped out prematurely. The intervention is a broad-based nutritional supplement of dietary nutrients, primarily chelated trace minerals and vitamins, administered in high doses. At study entry and periodically thereafter, patients were assessed with the Hamilton Rating Scale for Depression (HAM-D), the Brief Psychiatric Rating Scale (BPRS), and the Young Mania Rating Scale (YMRS).

Results: For those who completed the minimum 6-month open trial, symptom reduction ranged from 55% to 66% on the outcome measures; need for psychotropic medications decreased by more than 50%. Paired t tests revealed treatment benefit on all measures for patients completing the trial: HAM-D mean score at entry = 19.0, mean score at last visit = 5.4, t = 5.59, df = 9, p < 01; BPRS mean score at entry = 35.3, mean score at last visit = 7.4, t = 2.57, df = 9, p < .05; YMRS mean score at entry = 15. 1, mean score at last visit = 6.0, t = 4. 11, df = 9, p < .0 1. The effect size for the intervention was large (> .80) for each measure. The number of psychotropic medications decreased significantly to a mean SD of 1.0 1. 1 (t = 3.54, df = 10, p < .0 1). In some cases, the supplement replaced psychotropic medications and the patients remained well. The only reported side effect (i.e., nausea) was infrequent, minor, and transitory.

Conclusion: Some cases of bipolar illness may be ameliorated by nutritional supplementation. A randomized, placebo-controlled trial in adults with bipolar I disorder is currently underway, as well as open trials in children.

Solid scientific research shows that many dietary nutrients, including minerals and vitamins, are essential for normal brain function. For instance, deficient levels of various B vitamins are related to pathologic brain and behavior disorders ranging from Korsakoff's syndrome to pellagra. Recent work on folic acid (vitamin B,) suggests that low levels may be associated with depressive symptomatology and poor response to antidepressant medication. Less is known about the role of trace elements, but there is considerable evidence that these too may be essential for normal brain function. Zinc provides a good example. Most of the excitatory neurons of the cerebral cortex have glutamate as their primary transmitter. One type of glutaminergic neuron accumulates zinc within vesicles at axon terminals and releases it into the synapse upon firing. The precise roles of zinc in synaptic function are not known, although its presence is certain, and there are zinc-binding sites on one subset of glutamate receptor called the NMDA (N-methyl-D-aspartate) receptor. Zinc, copper, and magnesium all appear to play important modulatory roles in controlling the NMDA receptor, which has been implicated in various forms of cortical plasticity, including learning. It is possible, then, that decreased levels of some minerals in the brain may produce abnormal NMDA-mediated plasticity and subsequent abnormalities in behav-

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