Curcumin for Cognition—Does the Path Lie in the Cerebral Circulation?

Dear Editor:

We thank D'Cunha et al. (1) for their commentary “Curcumin for cognition: will it live up to the hype?” in which they cite recent publications in Advances in Nutrition by Lopresti (2) and ourselves (3). Considering the poor bioavailability of curcumin, Lopresti reviewed evidence to suggest that “curcumin's potential as a therapeutic agent may not solely rely on its bioavailability, but rather its medicinal benefits may also arise from its positive influence on gastrointestinal health and function.” Drawing on this, D'Cunha et al. (1) summarize multiple physiologic actions of curcumin and propose that direct gastrointestinal actions might account for at least some of its systemic efficacy, including cognitive benefits. However, despite growing interest in the “gut-brain axis,” a direct mechanistic link between gastrointestinal actions and cognitive effects has not yet been demonstrated.

In our review, we suggested an alternative pathway linking systemic actions of DHA and curcumin to cognitive performance and we described a clinical trial through which we are testing our hypothesis. We presented evidence for beneficial effects of both nutrients on microvascular function, mediated via the endothelium. Thus DHA and curcumin may act directly or indirectly (indeed via the gut) to suppress inflammatory, thrombotic, and/or vasoconstrictor mechanisms associated with impaired endothelial function. We propose that impaired endothelial function can undermine brain function and contribute to neurodegenerative changes by impeding cerebrovascular perfusion and disrupting the selective permeability of the blood-brain barrier.

We have obtained evidence that other vasoactive nutrients, e.g., resveratrol, may improve cognitive performance by enhancing the increase of cerebral blood flow in response to cognitive demands (4). In our review, we hypothesized that DHA and curcumin might similarly deliver cognitive benefits by enhancing endothelial vasodilator responsiveness in the cerebral microvasculature. The proposed clinical trial described in our review is now testing this hypothesis, which, if correct, would provide a mechanistic link between curcumin-induced reductions in systemic inflammation, whether initiated in the gut or in the circulation, and the purported cognitive benefits of curcumin.

D'Cunha et al. (1) propose that synergistic benefits of curcumin and DHA may result from improved gastric absorption of the latter in the presence of curcumin. They also argue that curcumin, by improving blood-brain barrier function, may facilitate accumulation of DHA in the brain. Although an interesting concept, this is not critical for our hypothesis in which both curcumin and DHA are proposed to benefit brain function by acting in the cerebrovasculature rather than in neural tissue. We are nevertheless pleased to see the active interest in testing mechanisms by which selected nutrients may benefit brain function and, in particular, the potential for identifying effective nutritional strategies to help counteract the rising prevalence of neurodegenerative diseases in our aging population.

Notes

The authors reported no funding received for this letter to the editor. Author disclosures: PRCH, JCK, and RHXW, no conflicts of interest.