Nitrate derived from vegetables lowers risk of dementia

A higher intake of dietary nitrate from vegetables appears to reduce the risk of dementia in the general population, suggests a study.

“We found no evidence for vascular brain health as an underlying mechanism,” the investigators said.

Using food-frequency questionnaires, the investigators assessed dietary intakes in 9,543 dementia-free participants (mean age 64 years, 58 percent female) from the prospective population-based Rotterdam Study between 1990 and 2009. They followed-up participants for dementia incidence until January 2020.

Cox models were used to examine the association between dietary nitrate intake and incident dementia. Linear mixed models and logistic regression models were also used to assess the association of dietary nitrate intake with changes in imaging markers across three consecutive examination rounds (mean interval between images 4.6 years).

The median dietary nitrate consumption was 85 mg/d, derived on average for 81 percent from vegetable sources. Of the participants, 1,472 developed dementia during a mean follow-up of 14.5 years. [Am J Clin Nutr 2023;118:352-359]

A higher intake of total and vegetable dietary nitrate significantly correlated with a reduced risk of dementia per 50-mg/d increase (hazard ratio [HR], 0.92, 95 percent confidence interval [CI], 0.87‒0.98 and HR, 0.92, 95 percent CI, 0.86‒0.97, respectively) but not with changes in neuroimaging markers.

Notably, nonvegetable dietary nitrate intake did not show an association with the risk of dementia (HR, 1.15, 95 percent CI, 0.64‒2.07) or with changes in neuroimaging markers.

In previous studies that examined the effect of nitrate or nitrite supplementation on cognitive performance, some showed improvements in certain cognitive test performances following supplementation, but most of these found no effect. [Nitric Oxide 2014;40:67-74; Aging (Albany NY) 2015;7:1004-1021; Nutrients 2022;14:1052; Nitric Oxide 2016;61:55-61; Food Funct 2014;5:849-858]

Mechanism

“Our findings of an association between a higher dietary nitrate intake and a lower risk of dementia could be explained by the free radical nitric oxide,” the investigators said.

“Oral bacteria metabolize dietary nitrate to nitrite, and in the acid environment of the stomach, nitrite can be metabolized further into nitric oxide. This will be absorbed in the small intestine and subsequently released in the blood circulation,” they added. [Nat Rev Drug Discov 2008;7:156-167]

Nitric oxide in the blood circulation is responsible for regulating vasodilation and platelet aggregation, which then maintains vascular health, a key determinant in dementia prevention. [Cardiol Res Pract 2020;20202617970; Circulation 1992;86:1302-1309; Biorheology 2014;51:121-134]

“However, our null findings with brain imaging markers could not confirm that vascular brain health drives the association between dietary nitrate intake and dementia,” the investigators said.

In connection to this, an earlier meta-analysis revealed no strong evidence for an acute effect of dietary nitrate intake on cerebral perfusion, which could be potentially explained by the fact that nitric oxide affects small blood vessels, which cannot be observed on brain images. [Crit Rev Food Sci Nutr 2019;59:2400-2410]

“Alternative potential mechanisms underlying the association between dietary nitrate and dementia include a protective effect of nitric oxide on metabolic functions and the regulation of reactive oxygen species homeostasis,” the investigators said. [Diabetes 2003;52:1270-1275; Proc Natl Acad Sci USA 2010;107:17716-17720; Cell Metab 2018;28:9-22]

“Further studies should verify our observations, elucidate the potential effects of nonvegetable dietary nitrate intake on brain health, and identify mechanisms underlying the association between dietary nitrate intake and the risk of dementia,” they added.