Caffeine With Nootropics: What Human Combination Trials…

What the evidence shows

One controlled human trial tested caffeine with L-theanine for short-term attention.
The combination improved some measures, while other attention measures did not change significantly.
A separate caffeine study found brain-activity changes, but not clear working-memory enhancement.
A chlorogenic-acid trial in patients with mild cognitive impairment did not report a caffeine pairing.

The main tested pairing: caffeine and L-theanine

For coffee with nootropics, the clearest tested pairing here is caffeine plus L-theanine. Acute effects of theanine, caffeine and theanine-caffeine combination on attention. In a five-way crossover trial, 20 healthy men received L-theanine (200 mg), caffeine (160 mg), their combination, one cup of black tea, or distilled water. The trial measured simple and recognition visual reaction times, brain-response measures, and visual and motor responses. A crossover trial compares different conditions in the same participants.

Attention results were not the same across measures

The trial reported significantly improved mean recognition visual reaction time after theanine (P = 0.019), caffeine (P = 0.043), and their combination (P = 0.001). It did not report significant improvement after black tea (P = 0.429) or distilled water (P = 0.822). Simple visual reaction time and visual- and motor-response latencies showed no significant differences between conditions. Brain-response N2-P300 amplitude was higher after theanine and caffeine than after distilled water (P = 0.001 for each). The combination produced higher amplitude than distilled water (P < 0.001), theanine (P = 0.029), and caffeine (P = 0.005). Researchers found no significant theanine-caffeine interaction for recognition reaction time or N2-P300 amplitude. The authors equated 200 mg of theanine with the amount in eight cups of black tea. They described the attention effects as possibly additive at high doses.

Caffeine alone changed brain activity in another study

A separate trial tested caffeine alone, not a nootropic pairing. The effect of caffeine on working memory load-related brain activation in middle-aged males. It included 20 healthy male habitual caffeine users aged 40 to 61. In a double-blind crossover design, they received 100 mg of caffeine or a dummy treatment. Participants had consumed their usual caffeinated products during the workday, ranging from 145 to 595 mg, and were not in withdrawal. Compared with the dummy treatment, caffeine increased activity in both dorsolateral prefrontal regions during working-memory encoding. It reduced activity in the left thalamus during maintenance. The authors linked these patterns to cognitive control during encoding and arousal-linked attention control during maintenance. Behavioral and brain findings fit a detrimental effect on working memory at higher loads more than an enhancement.

A chlorogenic-acid study does not establish another pairing

A controlled study of another coffee compound cannot establish a caffeine-nootropic combination. Effect of Chlorogenic Acids on Cognitive Function in Mild Cognitive Impairment: A Randomized Controlled Crossover Trial. The abstract describes a chlorogenic-acid beverage and a dummy beverage, but does not report a caffeine pairing. The trial included 34 patients with mild cognitive impairment. Participants drank a beverage containing 553.6 mg of chlorogenic acids per bottle twice daily for 12 weeks, then switched beverages after a four-week washout. They made significantly fewer errors on the TMT-B attention test during the chlorogenic-acid condition, but completion time did not differ. MMSE, ADAS-cog, and TMT-A scores also did not differ significantly between conditions. The authors said chlorogenic acids appeared to improve attention and executive function in this group.

What these studies leave uncertain

The combination trial measured short-term attention in 20 healthy men. The caffeine-only trial measured brain activity and working memory in 20 middle-aged male habitual users. The chlorogenic-acid trial studied 34 patients with mild cognitive impairment, not a reported caffeine pairing. These results apply to the tested groups and measures. They do not establish lasting benefits, effects in other groups, or benefits from other caffeine-nootropic combinations.

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About this article

NootroWorld publishes research summaries, not medical advice. This article describes what studies have and have not established; it does not tell you what to take. Supplements can interact with medication, pregnancy and existing health conditions, and study populations often differ from your own situation. Discuss any personal decision with a qualified healthcare professional.