AAN 2011: Trial Shows Slow-release Zinc Is Safe but Ineffective in Alzheimer's Disease

A new slow-release formulation of zinc is safe for Alzheimer's disease patients, and effectively raises serum zinc levels, but results from a pilot trial do not indicate it benefits cognition, according to a study presented at the 63rd Annual Meeting of the American Academy of Neurology.

The study compared a once-daily, gastro-retentive, sustained-release preparation of 150 mg zinc plus 100 mg L-cysteine (ReaZin) to placebo, given for six months.

The hypothesis that zinc might aid cognition is based in part on its relationship to dietary copper. Zinc lowers copper, and low zinc and high copper levels have been linked to cognitive deficits in both animal models and Alzheimer's disease patients.

Fifty-seven patients with Alzheimer's disease were enrolled in the trial, results from which were presented by Diana Pollock, MD, of the Martin Plant Neurosciences Institute in Clearwater, FL. Patients underwent baseline testing for blood levels of copper and zinc, plus cognitive testing with three different measures.

Forty-two patients completed the trial, with equal numbers of dropouts in the active treatment and placebo arms. The primary endpoint was the ability to safely alter zinc and copper levels, and at the end of the six-month treatment, patients receiving zinc had significantly lower serum copper, and significantly higher serum zinc.

The slow release of the zinc preparation was intended to reduce the high incidence of nausea, abdominal cramps, and vomiting seen with an FDA-approved zinc treatment used in Wilson's disease, a disorder of copper excess. In previous trials, the incidence of these side effects was 7% for the new preparation, versus 100% for the approved medication. Results from the current trial showed a similar level of tolerability, with no difference between placebo- and zinc-treated groups in gastrointestinal symptoms.

There was no significant difference between active treatment and placebo on any of the three cognitive tests. Scores on the ADAS-Cog (Alzheimer’s Disease Assessment Scale-Cognitive) remained roughly similar from baseline to study's end in both groups, as did the scores on the Clinical Dementia Rating Scale and the Mini-Mental State Exam.

Pollock noted that the relatively small sample size makes it difficult to draw firm conclusions about the effects of zinc therapy on cognition in Alzheimer's disease. The company developing the zinc supplement, Adeona Pharmaceuticals, which supported the study, is continuing to explore its potential in Alzheimer's disease, and further trials are planned.