No improvement in cognitive function with methylliberine supplementation Original paper

In this randomized controlled trial, supplementation with methylliberine, a metabolite of caffeine, did not improve cognitive function in comparison with a placebo.

This Study Summary was published on March 27, 2024.

Quick Summary

In this randomized controlled trial, supplementation with methylliberine, a metabolite of caffeine, did not improve cognitive function in comparison with a placebo.

What was studied?

The effect of methylliberine (ML) on mood and cognitive function.

Who was studied?

25 adults without any known health conditions (average age of 33.5; 13 women, 12 men).

All participants typically consumed less than 400 mg of caffeine per day and did not consume caffeine for 12 hours prior to testing.

How was it studied?

This randomized controlled trial used a crossover design in which all participants received the ML and a placebo for 4 days in a randomized order, with a washout period of at least 7 days between interventions.

Cognitive function and subjective mood were assessed prior to each supplementation period. The participants took their assigned intervention for 3 days. On the 4th day, testing was conducted prior to their assigned intervention and at 1, 2, and 3 hours afterward.

The Stroop test and Trail Making Test (TMT-B) were used to assess cognitive function. The Stroop test measures cognitive interference, attention, processing speed, cognitive flexibility, and working memory. The TMT-B primarily measures cognitive flexibility.

Visual analog scales were used to assess 12 subjective outcomes, including energy, sustained energy, focus, positive outlook, and resilience to stress.

Heart rate and blood pressure were also assessed.

What were the results?

No significant differences in cognitive function (Stroop test or TMT-B) were observed between ML and placebo groups after 3 days of supplementation. No significant differences in any of the subjective outcomes were observed between the ML and placebo groups in the primary analysis, which included adjustments for multiple comparisons to reduce the risk of false positive results.

A post hoc analysis found that positive outlook, well-being, and the ability to tolerate stress were improved to a greater degree 3 hours after ML in comparison with a placebo. A post hoc analysis also found that women had a greater increase in sustained energy both 1 and 3 hours after ML in comparison with a placebo, whereas men did not. It is unclear if the post hoc analyses included corrections for multiple comparisons, and caution may be appropriate when interpreting these findings.

No differences in heart rate or blood pressure were observed between groups after 3 days of supplementation. Higher diastolic blood pressure was observed in the placebo group 2 hours after supplementation on day 4, but heart rate, systolic blood pressure, and diastolic blood pressures were similar between groups at 3 hours postsupplementation.

Anything else I need to know?

This study was funded by Compound Solutions, the manufacturer of the ML supplement and was conducted at a facility owned by an ML patent holder. These represent notable financial conflicts of interest.

Because some participants may have experienced acute caffeine withdrawal during the test conditions on day 4, the improvements in well-being with ML may represent reductions in caffeine withdrawal symptoms.

This Study Summary was published on March 27, 2024.