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Effect of Caffeine Versus Placebo Supplementation On Blood Glucose Concentration
Summary
In twenty-two presumably healthy third year dental students blood-glucose levels after oral ingestion of 250 mg. caffeine were significantly higher than the blood-glucose levels in twenty-one students ingesting a placebo.
Introduction
There is increasing recognition of the diagnostic and possible prognostic significance of carbohydrate metabolism in seemingly non-diabetic syndromes such as multiple sclerosis (Cerkez and Chandler 1962), gout (Berkowitz 1966), carcinomatosis (Lisker et al. 1966), mental illness (Salzer 1966), periodontal disease (Cheraskin 1960), arteriosclerosis (Kingsbury 1966), and ischemic heart-disease (Gelfand and Fabrykant 1965).
Blood-glucose concentration, the most commonly employed barometer of carbohydrate metabolism, is the resultant of a host of hormonal and dietary factors. Surprisingly, despite the large consumption of caffeine-containing substances, little attention has been directed to the possible effects of caffeine on blood-glucose content. Deakins (1939) observed, from four glucose-tolerance tests performed on himself at different times with caffeine and coffee, that large doses of caffeine depress the peak of the curve and delay the return of blood-glucose to baseline values. He concluded, from these limited studies, that caffeine per se did not elevate blood-glucose appreciably. Bellet et al. (1965) studied the plasma-glucose values during a three-hour period following ingestion of coffee, water, caffeine sodium benzoate, and sodium benzoate. They reported that there were no significant changes in blood-glucose. Hankiewicz (1960) investigated the blood-sugar in 228 patients, including 176 diabetics, before and after administration of caffeine by injection and by mouth as caffeine sodium benzoate and coffee. He concluded that caffeine depressed blood-sugar and that the effect was related to the dose of the drug and to the blood-glucose concentration. lancu et al. (1957), however, observed in normal and cortically-inhibited children that caffeine produces varying degrees of hyperglycaemia. Jankelson et al. (1967) found, in nine volunteers with maturity-onset diabetes, blood-glucose levels (after intravenous glucose, 0.5 g. per kg. body-weight) significantly higher following two cups of “instant” coffee than when water had been drunk.
Because of the ubiquity of caffeine consumption, the diagnostic and prognostic potential of blood-glucose, and the varied published results, this study was designed to reinvestigate the relation of caffeine to blood-glucose in a sample of young and presumably healthy subjects.
Materials and Methods
Forty-three junior dental students presented themselves fasting at 10 A.M. A venous blood sample was obtained and blood-glucose measured (Nelson 1944, Somogyi 1945).
Immediately after the blood was drawn, the group was randomly divided. Twenty-two subjects were asked to swallow a capsule containing 250 mg. caffeine (U.S.P.) with 5 oz. of water; the remaining twenty-one took an indistinguishable placebo capsule containing lactose. Blood samples were again obtained half an hour and one and two hours later.
Results and Discussion
Table I shows the means and standard deviations for age of the volunteers and the blood-glucose values. There is no statistically significant difference of the means of the ages of the two groups (utilising the Student t test). With regard to blood-glucose, the half-hour and the two-hour levels are statistically significantly different (P<0.050 and < 0.005), and the one-hour level borders on statistical significance at the 5% confidence level. In other words, the mean blood-glucose at a half and two hours after caffeine ingestion is significantly higher than for the placebo group.
Table I–Statistical Significance of Caffeine-Versus-Placebo Supplementation on the Blood-Glucose Concentration
| — | Placebo group | Caffeine group | Significance of differences of means |
| Age (yr.)
Blood-glucose: Fasting ½ hr. 1 hr. 2 hr. |
24.9 ± 3.5
86.1 ± 6.1 86.1 ± 6.3 86.3 ± 8.1 85.9 ± 7.5 |
26.8 ± 5.5
87.1 ± 6.9 90.1 ± 6.4 90.7 ± 6.2 93.0 ± 6.8 |
P > 0.100
P > 0.500 P < 0.050* P > 0.050 P < 0.005* |
*Statistically significant.
The remaining question is whether there were significant changes within the groups with the passage of time. Table II shows that, in the placebo group, there are no significant variations when the fasting mean blood-glucose is compared with the findings at a half, one, and two hours. In contrast, it is clear that the blood-glucose two hours after caffeine supplementation is significantly higher than that under fasting conditions. (A comparison of the fasting and one-hour scores borders on significance at the 5% confidence level.)
Table II–Statistical Significance of the Differences of the Means
| Group | Fasting blood-glucose versus: | ||
| ½ hr. | 1 hr. | 2 hr. | |
| Placebo
Caffeine |
P > 0.5000
P > 0.1000 |
P > 0.5000
P > 0.0500 |
P > 0.5000
P < 0.0005* |
* Statistically significant.
As the figure shows the mean blood-glucose values in time following the placebo supplement are strikingly steady. Thus the means are consistently close to 86 mg. per 100 ml. and the standard deviations regularly cluster about 6-7 mg. per 100 ml. The importance of this homeostatic picture is underlined (table II) by the lack of a significant difference between the temporal points. In contrast, the mean blood-glucose scores in the caffeine-supplemented group rise slowly and significantly with time (table II and figure).
Effect of caffeine-versus-placebo supplementation on blood-glucose studied during a two-hour period.
Although the blood-glucose response to caffeine reported here is not of great magnitude, it may produce physiological reverberations. Luft et al. (1966) observed that a reduction in blood-glucose of less than 10 mg. per 100 ml. was accompanied by a significant elevation in plasma-human-growth-hormone and a significant increase in the urinary output of adrenaline.
Since coffee is consumed in large quantities throughout the lives of many, including those who may have a predisposition to maturity-onset diabetes, its effect on glucose homoeostasis should be carefully explored.
References Cited:
- Bellet, S., Kershbaum, A., Aspe, J. (1965) Archs. Intern Med. 116, 750.
- Berkowitz, D. (1966). J. Am. Med. Ass. 197, 117.
- Cerkez, C., Chandler, J. H. (1962) Dis. Nerv. Syst. 23, 377.
- Cheraskin, E. (1960) Pract. dent. Monogr.
- Deakins, M. (1939) Proc. Soc. Exp. Biol. Med. 40, 588.
- Gelfand, M. L., Fabrykant, M. (1965) Circulation, 32, 95.
- Hankiewicz, J. (1960) Polski Tygod. lek. 15, 742.
- lancu, A., Rancher, E., Fenesan, E., Nedeleu, A., Felia, D. (1957) Rom. Med. Rev. 1, 42.
- Jankelson, O. M., Beaser, S. B., Howard, F. M., Mayer, J. (1967) Lancet, i, 527.
- Kingsbury, K. J. (1966) ibid. ii, 1374.
- Lisker, S. A., Brody, J. L., Beizer, L. H. (1966) Am. J. Med. Sci. 252, 282.
- Luft, R., Cerasi, E., Madison, L. L., von Euler, U. S., Casa, L. D., Roovete, A. (1966) Lancet, ii, 254.
- Nelson, N. A. (1944) J. Biol. Chem. 153, 375.
- Salzer, H. M. (1966) J. Natn. Med. Ass. 58, 12.
- Somogyi, M. (1945) J. Biol. Chem. 160, 69.




