Plasma nutrient status of patients with Alzheimer's disease: Systematic review and meta-analysis

Alzheimers Dement. 2014 Jul;10(4):485-502. doi: 10.1016/j.jalz.2013.05.1771. Epub 2013 Oct 19.


Background: Alzheimer disease (AD) patients are at risk of nutritional insufficiencies because of physiological and psychological factors. Nutritional compounds are postulated to play a role in the pathophysiological processes that are affected in AD. We here provide the first systematic review and meta-analysis that compares plasma levels of micronutrients and fatty acids in AD patients to those in cognitively intact elderly controls. A secondary objective was to explore the presence of different plasma nutrient levels between AD and control populations that did not differ in measures of protein/energy nourishment.

Methods: We screened literature published after 1990 in the Cochrane Central Register of Controlled Trials, Medline, and Embase electronic databases using Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines for AD patients, controls, micronutrient, vitamins, and fatty acids, resulting in 3397 publications, of which 80 met all inclusion criteria. Status of protein/energy malnutrition was assessed by body mass index, mini nutritional assessment score, or plasma albumin. Meta-analysis, with correction for differences in mean age between AD patients and controls, was performed when more than five publications were retrieved for a specific nutrient.

Results: We identified five or more studies for folate, vitamin A, vitamin B12, vitamin C, vitamin D, vitamin E, copper, iron, and zinc but fewer than five studies for vitamins B1 and B6, long-chain omega-3 fatty acids, calcium, magnesium, manganese, and selenium (the results of the individual publications are discussed). Meta-analysis showed significantly lower plasma levels of folate and vitamin A, vitamin B12, vitamin C, and vitamin E (P < .001), whereas nonsignificantly lower levels of zinc (P = .050) and vitamin D (P = .075) were found in AD patients. No significant differences were observed for plasma levels of copper and iron. A meta-analysis that was limited to studies reporting no differences in protein/energy malnourishment between AD and control populations yielded similar significantly lower plasma levels of folate and vitamin B12, vitamin C, and vitamin E in AD.

Conclusions: The lower plasma nutrient levels indicate that patients with AD have impaired systemic availability of several nutrients. This difference appears to be unrelated to the classic malnourishment that is well known to be common in AD, suggesting that compromised micronutrient status may precede protein and energy malnutrition. Contributing factors might be AD-related alterations in feeding behavior and intake, nutrient absorption, alterations in metabolism, and increased utilization of nutrients for AD pathology-related processes. Given the potential role of nutrients in the pathophysiological processes of AD, the utility of nutrition may currently be underappreciated and offer potential in AD management.

Keywords: Calcium; Copper; Folate; Iron; Magnesium; Manganese; Omega-3 fatty acids (DHA and EPA); Selenium; Vitamin A; Vitamin B1; Vitamin B12; Vitamin B6; Vitamin C; Vitamin D; Vitamin E; Zinc.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Alzheimer Disease / blood*
  • Databases, Bibliographic / statistics & numerical data
  • Fatty Acids, Omega-3 / blood
  • Humans
  • Manganese / blood
  • Nutritional Status / physiology*
  • Vitamins / blood


  • Fatty Acids, Omega-3
  • Vitamins
  • Manganese