Mixed nuts improve brain insulin action in overweight/obese older adults

Older adults with overweight or obesity who regularly eat mixed nuts appear to have better brain insulin action in the occipital and frontal regions, which are involved in the modulation of metabolic and cognitive processes, reports a study. They also show improvements in intrahepatic lipid content and different cardiometabolic risk markers but not in peripheral insulin sensitivity.

“[T]he longer-term daily intake of mixed nuts for 16 weeks improved brain insulin action in occipital and frontal regions,” the researchers said. “Therefore, regional brain insulin resistance observed in older adults with overweight or obesity can be beneficially affected by intervention strategies, which may be important for the prevention of age-related metabolic diseases.”

Twenty-eight healthy adults (mean age, 65 years; body mass index, 27.9 kg/m²) participated in this randomized, single-blinded, controlled, crossover trial. They received either daily 60-g mixed nuts (15 g of walnuts, pistachio, cashew, and hazelnuts) or no nuts (control) for 16 weeks, separated by an 8-week washout period, and adhered to the Dutch food-based dietary guidelines.

During follow-up, the researchers evaluated brain insulin action by measuring the acute effects of intranasal insulin on regional cerebral blood flow (CBF) using arterial spin labelling magnetic resource imaging. They also evaluated the effects on peripheral sensitivity (oral glucose tolerance test), intrahepatic lipids, and cardiometabolic risk markers. [Am J Clin Nutr 2024;119:314-323]

No changes were seen in the participants’ body weight and composition. However, those who consumed mixed nuts exhibited better regional brain insulin action in five clusters located in the left (difference in CBF responses to intranasal insulin: -4.5 mL/100 g/min; p<0.001; -4.6 mL/100 g/min; p<0.001; and -4.3 mL/100 g/min; p=0.007) and right occipital lobes (-4.3 and -3.9 mL/100 g/min; p=0.028) than controls.

“A fifth cluster was part of the left frontal lobe (-5.0 mL/100 g/min; p<0.001),” the researchers said, adding that mixed nuts intake did not improve peripheral insulin sensitivity.

Furthermore, participants in the mixed nuts arm had lower intrahepatic lipid content (-0.7 percentage point; 95 percent confidence interval [CI], -1.3 to -0.1; p=0.027), serum low-density lipoprotein cholesterol concentration (-0.24 mmol/L; 95 percent CI, -0.44 to -0.04; p=0.019), and systolic blood pressure (‒5 mm Hg; 95 percent CI, -8 to -1; p=0.006).

“Underlying mechanisms of nut consumption on brain insulin signalling are not known,” according to the researchers.

In a previous trial involving male adults with abdominal obesity, acute inorganic nitrate intake, which is known to increase nitric oxide bioavailability, contributed to higher CBF responses to nasal insulin in regions involved in the default mode network. [NeuroImage Clin 2022;35103115]

“We already reported that mixed nut consumption improved vascular function of frontal and parietal regions, which may relate to the beneficial effects observed on cognitive performance,” the researchers said. “In [the current] study, we showed that insulin responsiveness improved in other brain regions important for the modulation of metabolic processes.” [Clin Nutr 2023;42:1067-1075]

“Further intervention studies are needed to elucidate mechanisms underlying the effects observed on brain insulin responsiveness and investigate whether our findings can be extrapolated to other population groups,” the researchers said.