Crocus sativus L. (saffron) appears to own neuroprotective effects on cognitive impairment
in patients with Alzheimer’s disease (AD). The purpose of this work is to review evidence
and mechanisms of saffron-induced therapeutic outcomes and measureable cognitive benefits in
The literature was reviewed, and preclinical and clinical studies were identified. In vitro and in
vivo preclinical studies were selected according to these criteria: 1) development of saffron pharmacological
profile on biological or biophysical endpoints; 2) evaluation of saffron efficacy using animal
screens as an AD model, and 3) duration of the studies of at least 3 months. As for the clinical
studies, the selection criteria included: 1) patients aged ≥ 60, 2) AD diagnosis according to National
Institute on Aging-Alzheimer's Association (NIAAA) criteria, and 3) appropriate procedures to
assess cognitive, functional, and clinical status. A total of 1477 studies published until November
2020 were identified during an initial phase, of which 24 met the inclusion criteria and were selected
for this review.
Seventeen in vitro and in vivo preclinical studies have described the efficacy of saffron on cognitive
impairment in animal models of AD, highlighting that crocin appears to be able to regulate glutamate
levels, reduce oxidative stress, and modulate Aβ and tau protein aggregation. Only four clinical
studies have indicated that the effects of saffron on cognitive impairment were not different
from those produced by donepezil and memantine and that it had a better safety profile.
Saffron and its compounds should be further investigated in order to consider them a safer alternative
in AD treatment.