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How Do You Like Your Coffee?

Two studies shed light on our reactions to our morning coffee. Individuals vary in their sensitivity to caffeine, withdrawal symptoms when deprived of caffeine, and their caffeine tolerance.

The first report examined patterns of total caffeine consumption, caffeine intoxication (i.e., feelings of illness or jitteriness associated with caffeine consumption), tolerance, and withdrawal symptoms (headache, fatigue, anxiety, depression, nausea, or vomiting associated with attempts to reduce consumption) among 1,937 members of female-female twin pairs. Heritabilities for toxicity, tolerance, and withdrawal accounted for 35% to 45% of the variance between twins. Heritability for heavy caffeine use accounted for 77% of the variance between twins.

The second study used proton echo-planar spectroscopy to examine the responses to caffeine ingestion (10 mg/kg) of 9 heavy caffeine users and 9 caffeine-intolerant individuals. Compared with the heavy-use group, the caffeine-intolerant group developed moderate to marked symptoms of anxiety and physiologic arousal when dosed with caffeine, and their spectroscopy scans indicated significant increases in brain lactate levels both globally and specifically in the right insula, right temporal lobe, left frontal cortex, and left thalamus. After a one- to two-month caffeine holiday, 5 of the heavy users were restudied. Although only 1 responded to caffeine rechallenge with physiological arousal, all 5 showed caffeine-induced brain lactate increases comparable to those in the caffeine-intolerant group.

Comment: Heritability factors associated with caffeine use, intoxication, tolerance, and withdrawal qualitatively resemble genetic factors associated with nicotine, ethanol, cocaine, and cannabis use. In the caffeine-intolerant, reduced regional cerebral blood flow, resulting from caffeine's vasoconstricting effects, may lead to increased glycolysis and brain lactate production and consequently to the experience of anxiety. Adenosine and adrenergic receptors have also been implicated. But increased brain lactate is probably not directly responsible for feelings of anxiety; brain lactate increased in rechallenged heavy users, even in the absence of psychologic or physiologic distress.

— J Yager

Published in Journal Watch Psychiatry April 1, 1999

Citation(s):

Kendler KS and Prescott CA. Caffeine intake, tolerance, and withdrawal in women: A population-based twin study. Am J Psychiatry 1999 Feb 156 223-228.

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• Medline abstract (Free)

Dager SR et al. Human brain metabolic response to caffeine and the effects of tolerance. Am J Psychiatry 1999 Feb 156 229-237.

• Original article (Subscription may be required)
• Medline abstract (Free)