Journal Publication Summary:
Journal of Clinical Psychiatry Articles
December 6, 2001 Edition

Read the abstract on the National Library of Medicine website or read the editorial review of the actual Journal articles below.

Summary of Journal Articles

The idea that effective mood stabilization can be achieved through the use of vitamins, trace elements and amino acids is advanced in a study conducted by a team of researchers from the University of Calgary, Alberta's Faculty of Medicine. The results of the ongoing study are published in the latest edition of the Journal of Clinical Psychiatry. The same edition also contains a commentary by Dr. Charles Popper, MD, a psychopharmacologist from Harvard University . Dr. Popper also has patients in his clinical practice who are taking the nutritional supplement.

The subject of the research is Empowerplus, a nutritional supplement formulated by the Synergy Group of Canada Inc.

In an Abstract entitled: ‘Effective Mood Stabilization with a Chelated Mineral Supplement: An Open-Label Trial in Bipolar Disorder” , the study's author, Bonnie J. Kaplan, PhD, explains the therapeutic benefit of the use of a nutritional supplement to treat bipolar disorder. Dr. Kaplan is a research psychologist who studies mood and behavioral disorders and a Professor in the Department of Pediatrics, University of Calgary . She is also Director of the Behavioral Research Unit at the Alberta Children's Hospital.

Dr. Kaplan and colleagues at the University of Calgary , along with Dr. Richard C. Ferre ( Salt Lake City , Utah ), conducted a 6-month open-label trial with 14 patients diagnosed with bipolar disorder, aged 19-46 years, who were taking an average of 2.7 psychotropic medications each at study entry.

The intervention is a broad-based nutritional supplement (Empowerplus) of dietary nutrients; primarily trace minerals and vitamins, administered in high doses. The supplement has 36 ingredients, 33 of which are natural dietary minerals and vitamins including calcium, iron, magnesium, zinc, copper, potassium, and various vitamins such as A, C, D, E, and several B vitamins.

At study entry and periodically thereafter, patients were assessed with the Hamilton-Depression Scale (Ham-D), Brief Psychiatric Rating Scale (BPRS), and the Young Mania Rating Scale (YMRS). The results of the study demonstrated symptom reductions ranging from 55% to 66% on the outcome measures, while the need for psychotropic medications decreased by more than 50%.

Dr. Kaplan wrote about the outcomes: “The effect size for the intervention was large (>.8) for each measure and the number of psychotropic medications decreased significantly to a mean of 1.0 (from 2.7). In some cases, the supplement has replaced psychotropic medications and the patients have remained well. Side effects (i.e., nausea) have been infrequent, minor, and transitory.”

Based on these findings, Dr. Kaplan concludes: “Some cases of bipolar illness may be ameliorated by nutritional supplementation.”

“We have seen significant improvement in the mental health of the participants taking part in this study,” says Kaplan. “Our early findings certainly warrant further exploration of this supplement as a new treatment for mood and temper problems. In fact, a randomized, placebo-controlled trial in adults with bipolar I disorder is currently underway , two more have been funded, and we have completed some open trials in children,” she added.

In an article that accompanied the research, Dr. Kaplan provided an overview of the study's methodology, as well as a discussion of the various factors relevant to the impact of the nutritional supplement on behavior. She made the following points:

• “Solid scientific research shows that many dietary nutrients, including minerals and vitamins, are essential for normal brain function… 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…”

• “The evidence supporting the importance of minerals and vitamins in central nervous system functioning provided some scientific support for our interest in studying a supplement that is gaining considerable clinical attention in Canada and in many areas of the United States. Described herein are the data collected in open trials of the first, consecutive and unselected 11 cases of bipolar disorder in adults evaluated on this supplement and followed for at least six months, testing the hypothesis that a broad-based nutritional supplement that emphasizes trace minerals would help stabilize mood.”

• “We have been exploring the possible clinical benefit of a broad-based nutritional supplement consisting of 36 items, primarily minerals. The data reported here provide the first, preliminary scientific validation of the supplement's efficacy, and suggest that further research is warranted. “

• “Although much additional research is needed…our preliminary data and the general clinical experience of psychiatrists who are monitoring patients in our trials indicate that the supplement has a beneficial psychotropic effect and is not acting in only an adjunctive manner.”

• “No problematic adverse effects were encountered from the nutrient supplement. Patients generally reported a subjective sense of improved well being when taking the supplement, and several patients described this well-being as feeling more normal than what they had experienced with psychotropic medication. “

• “Regardless of the mechanisms involved, the findings reported here suggest that the amelioration of mood instability with broad spectrum nutritional interventions warrants further exploration.”

In his commentary on Dr. Kaplan's research, Dr. Charles Popper shared his observations from his clinical practice:

“My interest in this nutrient mixture was initially sparked by a case in my clinical practice. A 10-year-old with bipolar disorder was referred for treatment of severe temper tantrums, which had lasted for two to four hours daily for four months. The well-nourished child had no prior psychiatric history or treatment. After 2 days on the nutrients, his tantrums showed significant improvement, with the father-psychiatrist reporting a "complete" absence of outbursts or even irritability at 5 days. After 2 weeks, the available supply of the nutrient supplement was exhausted, and tantrums returned within 48 hours. A similar supplement, containing most of the same ingredients, was then started and produced a moderate improvement, which parents and teachers estimated as 60% of the original effect. When restarted on the original formula, the symptoms were judged to have again responded completely. This naturalistic A-B-A-C-B trial caught my attention because of the full stabilization without psychiatric medications and the absence of observed adverse effects.”

“I proceeded to cautiously conduct additional trials of the Hardy-Stephan nutrient supplement. Among 22 patients who clinically met criteria for bipolar disorder, 19 cases showed what I judged to be a positive response (2 mild, 7 moderate, 10 marked improvement). Among the 15 drug-treated patients, 11 patients have been stable for 6-9 months without psychiatric medications. These observations are consistent with Kaplan's open-label findings…”

The fact that Dr. Popper's results were consistent with Dr. Kaplan's is indeed encouraging news, particularly since his symptom reduction rate was 86%, with a significant percentage of drug-treated patients (73%) stable, without psychiatric medications.

Dr. Popper also calls for more study into ‘nutrition-behavior' reactions. “Even allowing for the usual overestimation of effects in open-label series, these preliminary findings raise interesting questions about nutrition-behavior interactions. Kaplan's open-label report justifies her now on-going controlled study, whose outcome appropriately precedes pursuing questions of mechanism of action and parsimony.”

“(My) observations are consistent with Kaplan's open-label findings, but leave open questions of safety. Even though it contains only "natural" ingredients and is not under FDA purview, the Hardy-Stephan nutrient supplement should be examined in controlled empirical research -- just as new pharmacological agents are -- to properly assess adverse effects and potential risks. Psychiatrists do not normally think of vitamins or minerals as modifiers of the effects of psychiatric medications, but the early anecdotal experience with this nutrient supplement suggests that there may be strong micronutrient-medication interactions. This mineral-vitamin supplement seems to generally potentate the clinical properties of psychiatric drugs. Most patients in Kaplan's study could be managed with less medication after the nutrient supplement was added” he wrote.

Dr. Popper also signaled the need for more study into ‘transitioning' patients from medications to micronutrients. “In my observations, transitioning patients from medications to micronutrients is exceedingly tricky to manage. Introducing micronutrients too quickly can increase the adverse effects of medications, including agitation, while withdrawing psychiatric medications too quickly can result in symptom exacerbation. Often, both increased adverse effects and symptom resurgence are seen at once. Much more data is needed about how to "transition" patients who are currently taking psychiatric medications.“

Synergy welcomed these observations: ”Based on our knowledge and experience we fully concur with Dr. Popper's cautionary note. As the nutritional supplement normalizes the brain's chemistry, it is critical that clinicians and their patients be aware of these interactions. That is why we consistently urge participants to work with their clinicians in order to ensure safe and effective monitoring. We strongly recommend that those desiring to reduce or eliminate psychotropic medications be under competent medical supervision,” they said.

In closing his article, Dr. Popper said: “If Kaplan's preliminary findings are confirmed in controlled research, and if safety studies are favorable, what then? What if some psychiatric patients could be treated with inexpensive vitamins and minerals rather than expensive patented pharmaceuticals? Or if some doses of psychiatric drugs could be reduced by the concurrent use of nutrients? The economic implications, for individual patients and for the pharmaceutical industry, are difficult to overlook. For now, micronutrient treatments and other nutritional approaches remain in a very early scientific stage of investigation. Depending on how this line of research develops, clinicians and researchers may need to re-think the traditional bias against nutritional supplementation as a potential treatment for major psychiatric disorders.”

David Hardy and Tony Stephan responded to the study results: “This study is an important step in the evolution of our efforts to help the mentally ill. While we have seen similar results with the participants in our open-label series, we knew it was crucial to the supplement's wider legitimacy to have its performance measured and scrutinized in a scientific setting. We are grateful to the University of Calgary and to Dr. Popper for taking the time to study the supplement's impact on the mentally ill. The decision to research the supplement was entirely theirs and the beneficiaries of this work will be the mentally ill.”