Theobromine for improved cognitive function? Original paper

Age-related cognitive decline is a serious problem in older adults and is characterized by impairments of memory and attention. Lifestyle interventions such as exercise, a healthy diet, or the consumption of certain dietary compounds can help to counteract the symptoms of age-related cognitive decline.^[1] For instance, previous studies have reported a neuroprotective effect of dark chocolate.^[2][3] Can theobromine — the primary active compound in cacao — explain the neuroprotective effects of chocolate?

This cross-sectional study in 2,845 American older adults (average age of 70) examined whether a high intake of dietary theobromine (via cacao or other sources) was associated with improved cognitive function. For this purpose, the researchers compared the cognitive function of participants with the highest dietary theobromine intake (≥43 mg per day) to the cognitive function of those with lower theobromine intakes (<43 mg per day).

Cognitive function was assessed using three cognitive tests: (i) the word learning and recall test, which measures immediate and delayed learning abilities; (ii) the animal fluency test, which measures executive function and verbal fluency; and (iii) the digit symbol substitution test, which measures processing speed, sustained attention, and working memory.

The researchers adjusted the analyses for potential confounders, including participant characteristics (e.g., age, sex, and education), lifestyle factors (e.g., smoking status, caffeine consumption, and BMI), and history of disease (e.g., stroke, diabetes, and hypertension). Additionally, they also performed subgroup analyses to investigate how potential confounders influenced the outcomes.

The participants with the highest intake of dietary theobromine (≥43 mg per day) had improved cognitive function compared to those with lower theobromine intakes (<43 mg per day) in terms of 4% higher executive function and verbal fluency and 6% higher processing speed, sustained attention, and working memory. However, there were no differences in immediate and delayed learning abilities.

The outcomes remained unchanged after adjusting for potential confounders. However, in the subgroup analyses, the researchers found that caffeine intake influenced the outcomes of participants with high theobromine intakes. The participants with higher-than-median caffeine intakes (≥102 mg per day) showed higher cognitive function than those with lower caffeine intake (<102 mg per day).

The threshold for a high theobromine intake in this study was defined as 43 mg per day. This amount corresponds roughly to 5 grams or half a square of dark chocolate per day.

Given the cross-sectional design of this study, no causal relationship between theobromine and cognitive function can be inferred from these results. To establish such a causal link, ​randomized controlled trials are needed, and a few such studies have already been published, with promising preliminary evidence that such a causal link may in fact exist.^[3]​​​​​​​​^[4]