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Caffeine and exhaled nitric oxide
  1. T J Warke1,
  2. M D Shields1,
  3. J Finnegan2,
  4. M D Shields2
  1. 1Department of Child Health, The Queen’s University of Belfast, Belfast BT12 6BJ, UK
  2. 2Royal Belfast Hospital for Sick Children, Belfast, UK
  1. Correspondence to:
    Dr M D Shields, Department of Child Health, The Queen’s University of Belfast, Belfast BT12 6BJ, UK;
  1. P S Thomas3,
  2. D H Yates3,
  3. C Bruce3
  1. 3Faculty of Medicine, University of New South Wales, NSW 2052, Australia; paul.thomas{at}

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We read with interest the paper by Bruce et al1 which reported a significant decrease in exhaled nitric oxide (NO) levels 1 hour after caffeine consumption. However, we do not believe that this study has fully clarified the relationship between caffeine consumption and exhaled NO levels.

When ascertaining the normal ranges for offline exhaled NO measurements we observed that some individuals had raised exhaled NO levels after caffeine consumption. To further clarify this effect, exhaled NO (parts per billion (ppb)) levels were measured at baseline and 0.5 and 1 hour after drinking a hot cup of coffee in 18 healthy non-asthmatic adults (five men) aged 17–56 years. Exhaled NO was measured by chemiluminescence (NOA 280, Sievers Instruments Inc, Boulder, CO, USA) using an offline technique in which subjects performed a slow vital capacity manoeuvre into a mylar balloon against a resistance of 5 cm H2O which corresponded to a flow rate of 50 ml/s. In order to minimise NO contamination from the upper airways and dead space, the first portion of the exhalation was not collected. Median (interquartile range) levels of exhaled NO were significantly increased from baseline values 0.5 hour after caffeine consumption (8.3 (4.5–21.8) ppb v 5.4 (3.2–8.5) ppb, difference between medians 2.9 ppb (95% CI 1.4 to 12.4), p=0.007). There was no significant difference between baseline levels and the levels 1 hour after caffeine consumption (4.7 (2.6–6) ppb, p=0.4).

We conclude that levels of exhaled NO are significantly increased compared with baseline values 0.5 hour after caffeine consumption and have returned to baseline levels by 1 hour. The mechanism for this remains unclear. These results may need to be taken into consideration alongside the results of the previously mentioned study1 when designing studies and interpreting exhaled NO levels in adults.


Authors’ reply

We thank Warke et al for their interest in our paper and for publicising their results. This disparity in the effect of coffee between the two studies is not easy to explain. Although the sex ratio was similar, our study differed in the following ways: it was measured online, it was placebo controlled, showed that caffeine alone was the active ingredient, and our subjects had less heterogeneity in baseline levels of exhaled NO than those of Warke et al.1 In addition, we used freshly brewed coffee, measuring both the caffeine content and the serum plasma caffeine levels. Warke et al did not estimate the caffeine content of their coffee which would have been important, especially as instant coffee can have very low levels.2 We eschew instant coffee, and this may account for the difference. Whatever the cause of such a difference, it appears that coffee consumption can affect exhaled NO levels at either of the antipodes, perhaps in opposite directions.


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