British Journal of Nutrition

Systematic Review

Copper and iron in Alzheimer's disease: a systematic review and its dietary implications

Martin Loefa1a2 and Harald Walacha1a2 c1

a1 European University Viadrina, Institute of Transcultural Health Studies, Große Scharrnstraße 59, 15230 Frankfurt (Oder), Germany

a2 Samueli Institute, European Office, Frankfurt (Oder), Germany


Fe and Cu could represent dietary risk factors for Alzheimer's disease (AD), which has become a global health concern. To establish the relationship between diets high in Cu and Fe and cognitive decline or AD, we have conducted a systematic review of the literature (up to January 2011). We identified two meta-analyses, two systematic reviews, eleven placebo-controlled trials, five observational studies, forty-five case–control studies, thirty autopsy and five uncontrolled studies, and one case report. There were eleven interventional trials that tried to either supplement or deplete Fe and Cu, but none of them provided clear evidence of a beneficial effect on cognitive performance in patients with AD. The prospective studies revealed an association between a diet simultaneously high in SFA and Cu and cognitive decline. Case–control and autopsy studies showed elevated Fe levels in the brains of AD patients, whereas the evidence was less consistent for Cu. In most of the studies, Cu concentrations were unchanged in the cerebrospinal fluid and the brain but increased in the serum. In conclusion, the existing data suggest that diets excessive in Fe or Cu, together with a high intake of SFA, should be avoided in the elderly who are not at risk of anaemia. Basic studies and, building on this, clinical investigations are needed to further elucidate in which dietary patterns and in which patient groups an Fe- and Cu-rich diet might foster the risk of developing AD.

(Received February 09 2011)

(Revised May 10 2011)

(Accepted June 12 2011)

(Online publication July 18 2011)


c1 Corresponding author: H. Walach, fax +49 335 5534 2348, email

Abbreviations: Aβ, amyloid β protein; ADAS-cog, Alzheimer's disease assessment scale-cognitive subscale; AD, Alzheimer's disease; APP, amyloid β precursor protein; CSF, cerebrospinal fluid; DFO, desferrioxamine; HFE, haemochromatosis; MMSE, Mini Mental State Examination; TF, transferrin