Regular intake of dietary choline and betaine results in moderate short-term improvements in cognitive function and helps prevent cognitive decline in older adults with overweight or obesity and metabolic syndrome (MetS), reveals a study.
“[O]ur results suggest that higher daily dietary choline and betaine intake over time may be associated with modest favourable changes in cognitive function and may help to mitigate cognitive decline at short term in older adults with overweight/obesity and MetS,” said the investigators, who performed a secondary analysis nested within the PREDIMED-Plus trial.
A total of 6,610 older adults aged 55‒75 years with MetS were included in the analysis. A validated 143-item food frequency questionnaire was used to estimate dietary choline and betaine intake at baseline, 1, and 2 years. Cumulative averages were then calculated.
The investigators assessed cognitive function at baseline and 2 years using five composite scores based on eight neuropsychological tests covering global cognition, general cognition, attention, executive function, and language. They also explored the associations between energy-adjusted cumulative average intakes and 2-year cognitive changes using multivariable-adjusted linear regression models.
Each 1-mg/day higher energy-adjusted cumulative average dietary choline intake correlated with slower decline in attention (β, 5.20 × 10−4, 95 percent confidence interval (CI), 1.61 × 10−4 to 8.79 × 10−4; p=0.005) and improvements in language (β, 3.79 × 10−4, 95 percent CI, 0.62 × 10−4 to 6.95 × 10−4; p=0.019) over a median follow-up of 2 years. [Am J Clin Nutr 2026;123:5101265]
Older adults in the highest choline tertile had greater 2-year improvements in attention (β, 7.50 × 10−2, 95 percent CI, 2.12 × 10−2 to 12.88 × 10−2; ptrend=0.006) and language (β, 5.82 × 10−2, 95 percent CI, 1.04 × 10−2 to 10.59 × 10−2; ptrend=0.016) than those in the lowest tertile.
Likewise, each 1-mg/day higher betaine intake resulted in more favourable changes in executive function (β, 7.48 × 10−4, 95 percent CI, 1.71 × 10−4 to 13.20 × 10−4; p=0.011) and language (β, 9.13 × 10−4, 95 percent CI, 2.96 × 10−4 to 15.31 × 10−4; p=0.004).
Older adults in the highest betaine tertile showed greater 2-year improvements in language (β, 4.71 × 10−2, 95 percent CI, 0.25 × 10−2 to 9.17 × 10−2; ptrend=0.036) than those in the lowest tertile.
Mechanism
“Several hypotheses have been proposed to explain the potential relationship between dietary choline and betaine intake and cognition,” said the investigators.
Choline potentially improves cognitive function by functioning as a precursor of acetylcholine and phosphatidylcholine and through betaine-mediated methylation pathways involved in homocysteine remethylation and S-adenosyl-methionine formation. [Nutrients 2024;16:2845; Front Immunol 2025;16:1617077]
On the other hand, higher choline intake appears to increase Trimethylamine N-oxide, a gut microbiota-derived metabolite potentially linked to cognitive decline. However, its neurodegenerative role remains unclear and microbiota-dependent, which is why choline may be neuroprotective and yet carry some metabolic risks as well. [Am J Clin Nutr 2022;116:1201-1207]
“In contrast, betaine may confer neuroprotection through osmoprotective, methyl-donor, antioxidant, anti-inflammatory, and mitochondrial-supporting actions,” the investigators said. [Bio Multidiscip 2021;10:456]
“Given the chronic inflammation and vascular dysregulation characteristic of metabolic syndrome, these cognitive associations may be amplified in metabolically vulnerable individuals, particularly among those with higher adherence to the Mediterranean diet,” they added. [Am J Clin Nutr 2022;116:1565-1579]
“Further research in this area aimed at increasing dietary choline and betaine intake in individuals at risk of cognitive impairment over a longer follow-up period is warranted, given the rapidly expanding elderly population and the absence of curative treatment for cognitive decline,” the investigators said.