Intake of copper has no effect on cognition in patients with mild Alzheimer's disease: A pilot phase 2 clinical trial

Journal of Neural Transmission (Impact Factor: 2.4). 08/2008; 115(8):1181-1187. DOI: 10.1007/s00702-008-0080-1
Source: PubMed


Disturbed copper (Cu) homeostasis may be associated with the pathological processes in Alzheimer’s disease (AD). In the present
report, we evaluated the efficacy of oral Cu supplementation in the treatment of AD in a prospective, randomized, double-blind,
placebo-controlled phase 2 clinical trial in patients with mild AD for 12months. Sixty-eight subjects were randomized. The
treatment was well-tolerated. There were however no significant differences in primary outcome measures (Alzheimer’s Disease
Assessment Scale, Cognitive subscale, Mini Mental Status Examination) between the verum [Cu-(II)-orotate-dihydrate; 8mg Cu
daily] and the placebo group. Despite a number of findings supporting the hypothesis of environmental Cu modulating AD, our
results demonstrate that oral Cu intake has neither a detrimental nor a promoting effect on the progression of AD.

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Available from: Thomas A Bayer
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    • "However, this hypothesis is not well thought out, since AD patients display none of the manifestations of copper deficiency, which are a very low serum copper, anemia and bone marrow depression, and myelopolyneuropathy neurologic syndrome. Another example is Kessler et al. (2008) who gave copper to AD patients, and claimed to see no worsening. They saw no improvement either, which disproved their hypothesis that patients were suffering from copper deficiency. "
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    ABSTRACT: Evidence will be presented that the Alzheimer's disease (AD) epidemic is new, the disease being very rare in the 1900s. The incidence is increasing rapidly, but only in developed countries. We postulate that the new emerging environmental factor partially causal of the AD epidemic is ingestion of inorganic copper from drinking water and taking supplement pills, along with a high fat diet. Inorganic copper can be partially directly absorbed and elevate the serum free copper pool. The Squitti group has shown that serum free copper is elevated in AD, correlates with cognition, and predicts cognition loss. Thus, our inorganic copper hypothesis fits well with the Squitti group data. We have also shown that AD patients are zinc deficient compared to age-matched controls. Because zinc is a neuronal protective factor, we postulate that zinc deficiency may also be partially causative of AD. We carried out a small 6 month double blind study of a new zinc formulation and found that in patients age 70 and over, it protected against cognition loss. Zinc therapy also significantly reduced serum free copper in AD patients, so efficacy may come from restoring normal zinc levels, or from lowering serum free copper, or from both.
    Full-text · Article · May 2014 · Frontiers in Aging Neuroscience
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    • "). Moreover, the supplementation of an oral therapy of copper to subjects with AD in a phase 2, proof of concept, clinical trial by Kessler et al., 2008 was unsuccessful [57]. Conversely , an extensive number of studies since 1990 demonstrated that the hypermetallation of amyloid-␤ peptides can cause oxidative stress, H 2 O 2 production, and A␤ plaques (reviewed in [56]). "
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    ABSTRACT: The fraction of copper not bound to ceruloplasmin seems altered in Alzheimer's disease (AD). We have addressed this notion evaluating all the studies carried out from 1996 until March 2013 by means of meta-analysis. We performed our analysis on diverse indices evaluating the relationship between copper and ceruloplasmin in general circulation, namely 'Non-Cp copper', '% Non-Cp copper', and 'Adjusted copper'. For Non-Cp copper and % Non-Cp copper, the correct stoichiometry between copper and ceruloplasmin (6-8 atoms of copper for each ceruloplasmin molecule) in healthy controls has been adopted as criterion for the study to be included in the meta-analysis evaluating data with the canonic Walshe's formula for Non-Cp copper. Copper to ceruloplasmin ratio (Cu:Cp), which is an internal quality control check for ceruloplasmin calibration, was used as an index of the actual stoichiometry in the specimens. Adjusted (Adj-Cp) copper, even though less reliable, was calculated, allowing the evaluation of all the studies selected. An additional meta-analysis of systemic total copper was re-calculated accounting for all the studies carried out from 1983 to March 2013. Ten studies were analyzed in the meta-analysis for Non-Cp copper and % Non-Cp copper reaching a pooled total of 599 AD subjects and 867 controls. For Adj-Cp copper, 14 studies were analyzed with a pooled total of 879 AD and 1,712 controls. 27 studies were considered for systemic total copper meta-analysis, with a pooled total of 1,393 AD and 2,159 controls. All the copper indices analyzed were significantly higher in AD subjects compared to healthy controls.
    Full-text · Article · Sep 2013 · Journal of Alzheimer's disease: JAD
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    • "A meta-analysis of 17 studies with 1425 subjects showed that AD patients have higher levels of serum copper than controls [91]. Copper dysfunction is thought to play a role in AD pathology [92]; however, data from a prospective, randomized, placebo-controlled trial with 68 subjects showed that oral copper supplementation had neither a detrimental nor a promoting effect on the progression of AD [93]. "
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    ABSTRACT: Alzheimer's disease (AD) is a progressive neurodegenerative disorder that accounts for the major cause of dementia, and the increasing worldwide prevalence of AD is a major public health concern. Increasing epidemiological studies suggest that diet and nutrition might be important modifiable risk factors for AD. Dietary supplementation of antioxidants, B vitamins, polyphenols, and polyunsaturated fatty acids are beneficial to AD, and consumptions of fish, fruits, vegetables, coffee, and light-to-moderate alcohol reduce the risk of AD. However, many of the results from randomized controlled trials are contradictory to that of epidemiological studies. Dietary patterns summarizing an overall diet are gaining momentum in recent years. Adherence to a healthy diet, the Japanese diet, and the Mediterranean diet is associated with a lower risk of AD. This paper will focus on the evidence linking many nutrients, foods, and dietary patterns to AD.
    Full-text · Article · Jun 2013
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