Noguchi K, Matsuzaki T, Sakanashi M, et al. Effect of caffeine contained in a cup of coffee on microvascular function in healthy subjects. J Pharmacol Sci. 2015;127(2):217-222.

Coffee (Coffea spp., Rubiaceae) consumption has been associated with reduced cardiovascular disease mortality. The mechanism that may cause this effect has not been established. Caffeine intake may have an effect on microvessels, which control tissue blood flow and systemic blood pressure. Such effects would at least partially explain the beneficial cardiovascular effects that are associated with coffee intake. The aim of this double-blind, placebo-controlled, crossover study was to evaluate if single ingestion of caffeine from a cup of coffee improves microvascular function in healthy subjects.  

A total of 27 healthy Japanese subjects (age 22-30 years; 13 men and 14 women) were recruited for the study conducted in Okinawa, Japan. Subjects who smoked or consumed medications were excluded from the study. Subjects were told not to consume caffeine at least 12 hours before the study.

Subjects consumed 150 mL of hot water with 2 g of instant coffee (Taster's Choice^®; Nestlé; Vevey, Switzerland) that was either with or without caffeine. After an interval of 2 days, subjects consumed the alternate coffee in a crossover manner. Blood pressure and heart rate were recorded at baseline and every 15 minutes after the subjects consumed coffee. Microvascular function was evaluated by measuring finger (tip of left index finger or thumb) blood flow using a laser Doppler flowmeter and by determining percent post-occlusive reactive hyperemia by measuring blood flow after inflating and deflating a cuff on the arm that blocked blood flow.

Venous blood samples were also collected before and 30 minutes after coffee intake in 5 subjects. The plasma caffeine and catecholamine levels were measured in the blood samples. Caffeine content was measured in the caffeinated and decaffeinated coffees, and it was confirmed that the caffeine content was markedly higher in the caffeinated coffee compared to the decaffeinated coffee (54.5 ± 3.4 mg and 1.37 ± 0.09 mg, respectively). There were no significant differences in plasma caffeine levels before subjects consumed either caffeinated or decaffeinated coffee. The plasma caffeine levels were significantly increased 30 minutes after coffee intake in the subjects that consumed caffeinated coffee (from 0.75 ± 0.85 to 1.57 ± 1.30 µg/mL; P<0.05) but not in those that consumed decaffeinated coffee (from 0.76 ± 0.57 to 0.77 ± 0.60 µg/mL).

There were no significant differences found in blood pressure, finger blood flow, vascular resistance, or heart rate at baseline. Subjects that consumed caffeinated coffee had slightly but significantly increased systolic, diastolic, and mean blood pressure (maximally by 2.7, 3.2, and 2.8 mmHg, respectively). Intake of caffeinated coffee also significantly reduced finger blood flow (P<0.01) and significantly increased vascular resistance (in comparison to decaffeinated intake; P<0.01). No significant effects were found in those consuming decaffeinated coffee.

Post-occlusive reactive hyperemia was found to be similar in all the subjects before they consumed caffeinated or decaffeinated coffee. Subjects that consumed caffeinated coffee had significantly enhanced post-occlusive reactive hyperemia of finger blood in comparison with subjects that consumed decaffeinated coffee (P<0.01). The plasma concentrations of norepinephrine and epinephrine, which are different types of catecholamines, were not significantly different in the subjects before they consumed coffee or 30 minutes after they consumed either type of coffee. Thus, the effects of microvascular function could not be attributed to these catecholamines.

The authors report this is the first study that has assessed the acute effects of caffeine intake from coffee by evaluating endothelial function in the finger microcirculation. The authors explain the slight increase in blood pressure and vascular resistance may be due to an increase in vascular tone that results from the adenosine antagonism of caffeine. They also suggest the percent increase of reactive hyperemia, an indicator of improved microvascular function, may be due to endothelium-derived hyperpolarizing factors (EDHF) rather than nitric oxide.

The authors also admit to several limitations to the current study, including the small sample size, short-term testing period, and lack of information on the menstrual cycles of female subjects, which could possibly influence finger blood flow response. Additionally, they suggest that future studies should include patients with cardiovascular disease as well as healthy subjects. More studies are warranted to evaluate the effects of caffeine and other compounds in coffee (that may synergize with caffeine) on microcirculation and cardiovascular health. These studies should address the current limitations and be conducted in a range of different populations, including different age groups, ethnicities, health conditions, and subjects with different abilities to metabolize caffeine.