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Cited by 135Coffee research and impactsDiet, Metabolism, and DiseaseMetabolism, Diabetes, and Cancer

The Glucose Intolerance Induced by Caffeinated Coffee Ingestion Is Less Pronounced than That Due to Alkaloid Caffeine in Men

Open access
Battram, Danielle S, Arthur, Rebecca, Weekes, Andrew, Graham, Terry E·2006·The Journal of Nutrition
DOI 10.1093/jn/136.5.1276
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Abstract

Although acute alkaloid caffeine (CAF) ingestion results in an impaired glucose tolerance, chronic coffee (RCOF) ingestion decreases the risk of developing type 2 diabetes. This study examines the hypothesis that CAF ingestion impairs glucose tolerance to a greater extent than RCOF and that the ingestion of decaffeinated coffee (DECAF) results in a positive effect. Eleven healthy males underwent 4 double-blinded randomized trials. Each trial included the ingestion of either: 1) CAF in capsule form (4.45 mg/kg body weight), 2) RCOF (4.45 mg/kg body weight caffeine), 3) dextrose (placebo, PL) in capsule form, or 4) DECAF (equal in volume to the RCOF trial), followed 1-h later by a 2-h oral glucose tolerance test. Blood samples were collected at baseline (-30), 0 (time of treatment ingestion), 60 (initiation of oral glucose tolerance test), 75, 90, 120, 150, and 180 min. Area under the curve for glucose and insulin were higher (P < or = 0.05) following CAF than both PL and DECAF and, although a similar trend (P = 0.07) was observed following RCOF compared with DECAF, the effect was less pronounced. Interestingly, DECAF resulted in a 50% lower glucose response (P < or = 0.05) than PL, suggesting that the effects of PL and DECAF on glucose tolerance are not the same. These findings suggest that the effects of CAF and RCOF are not identical and may provide a partial explanation as to why acute CAF ingestion impairs glucose tolerance while chronic RCOF ingestion protects against type 2 diabetes.

AI snapshot

Written from the paper’s full text.

TL;DR

In 11 healthy men, acute alkaloid caffeine (CAF) produced greater glucose intolerance than caffeinated coffee (RCOF) during a 2-h OGTT, despite similar caffeine doses. Decaffeinated coffee (DECAF) also produced a 50% lower glucose AUC than placebo, suggesting non-caffeine coffee components affect glucose tolerance.

Key findings

  • CAF increased glucose, insulin, and C-peptide AUCs vs PL and DECAF (P ≤ 0.05). Table values: glucose AUC 285 ± 40 vs 184 ± 40 (PL) and 90 ± 29 (DECAF) mmol/L·2 h; insulin 32,758 ± 4,082 vs 22,087 ± 3,050 and 20,544 ± 2,419 pmol/L·2 h; C-peptide 166 ± 15 vs 126 ± 14 and 106 ± 12 nmol/L·2 h.
  • RCOF was intermediate: glucose AUC 176 ± 48 and insulin AUC 26,763 ± 2,250; only trends vs DECAF for glucose (P = 0.06) and insulin (P = 0.09), and no difference vs PL. CAF glucose AUC was higher than RCOF (P ≤ 0.05).
  • DECAF glucose AUC was 50% lower than PL (90 ± 29 vs 184 ± 40; P ≤ 0.05), while insulin and C-peptide AUCs did not differ between PL and DECAF.
  • CAF, but not RCOF, raised FFA and glycerol in the first hour; epinephrine increased more with CAF and RCOF than PL/DECAF (delta 0–60 min: CAF +0.15, RCOF +0.11, PL −0.04, DECAF +0.02 nmol/L; P ≤ 0.05).

Methods

  • Double-blinded, randomized, 4-trial crossover in 11 healthy nonsmoking men (age 23.2 ± 0.6 y, weight 76.4 ± 1.9 kg, VO2max 51.8 ± 3.7 mL/kg/min, body fat 15.6 ± 2.3%).
  • Treatments: CAF capsule (4.45 mg/kg), RCOF providing 4.45 mg/kg caffeine, dextrose placebo capsule, or equal-volume DECAF; 1 h later a 2-h OGTT. Blood sampled at −30, 0, 60, 75, 90, 120, 150, and 180 min.
  • Analyses: repeated-measures ANOVA/Tukey; AUC by trapezoid; Matsuda-DeFronzo ISI; linear regressions for fitness/body fat vs AUCs.

Limitations

  • The paper does not include a formal limitations section. It states epinephrine was measured in only a subset (n = 6) for technical reasons, and that the ISI was calculated with whole blood glucose/serum insulin for treatment comparison only, not absolute values.
  • The paper states it cannot determine which coffee components or mechanisms explain the attenuated RCOF or DECAF glucose responses.
  • Evident from the text: small sample of healthy men only, acute single-dose design, and no direct measurement of chlorogenic acids/quinides; findings may not generalize to women, other body compositions, or type 2 diabetes.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1093/jn/136.5.1276

Cites

37 of 37 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 13 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Serum insulin AUC was higher following CAF than both PL and DECAF (P≤0.05).

    “CAF resulted in a greater serum insulin response (AUC, P # 0.05) than both PL and DECAF.”
    Quote in the paperSubstantial claim
  • Findingown data

    Blood glucose AUC was higher with CAF than both PL and DECAF (P≤0.05).

    “the AUC for blood glucose (P # 0.05) was also higher with CAF than with both PL and DECAF (Table 1).”
    Quote in the paperSubstantial claim
  • Findingown data

    CAF resulted in a higher C-peptide AUC than RCOF (P≤0.05).

    “In addition, CAF resulted in a higher C peptide AUC (P # 0.05) than RCOF.”
    Quote in the paperSubstantial claim
  • Findingown data

    The change in epinephrine concentration from 0 to 60 min was higher for CAF and RCOF than for PL and DECAF (P≤0.05).

    “analysis of epinephrine concentrations during the first hour following treatment ingestion (the delta between 0 and 60 min) revealed that both CAF (1 0.15 nmol/L) and RCOF (1 0.11 nmol/L) resulted in higher elevations in epinephrine concentrations than with both PL (20.04 nmol/L) and DECAF (1 0.02 nmol/L) (P # 0.05).”
    Quote in the paperNot a substantial claim
  • Findingown data

    Following CAF and RCOF ingestion, epinephrine concentrations increased significantly, with values at 60, 120, and 180 min higher than baseline.

    “following the ingestion of CAF and RCOF, epinephrine concentrations increased significantly, such that values at 60, 120, and 180 min were higher than those observed at baseline.”
    Quote in the paperNot a substantial claim
  • May combine two claims. 20
  • The quote only partly states this claim. 4
  • Classified as probably not a substantial claim. 13

  • May combine two claims. The quote only partly states this claim.

    Findingown data

    Plasma caffeine concentrations were higher in RCOF than CAF at all time points, despite an absolute difference of only 2-4 μmol/L.

    “A treatment effect (P # 0.05) occurred between RCOF and CAF (RCOF .CAF) at all time points, despite the fact that the absolute difference in caffeine concentration was only 2-4 mmol/L.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    Body composition (% body fatness) or fitness (VO2max) were not correlated with AUC for glucose, insulin, or C-peptide during the OGTT for any treatment.

    “Body composition (% body fatness) or level of fitness (VO 2 max ) were not correlated with the AUC for glucose, insulin, or C peptide during the OGTT for any of the treatments (data not shown).”
    Quote in the paperNot a substantial claim

  • The quote only partly states this claim.

    Findingown data

    CAF resulted in a rapid increase in serum FFA concentrations of ~500 μmol/L during the first 60 min post-capsule ingestion (P≤0.05).

    “In contrast, CAF resulted in a rapid increase in FFA concentrations of ;500 mmol/L during the first 60 min postcapsule ingestion (P # 0.05).”
    Quote in the paperNot a substantial claim

  • The quote only partly states this claim.

    Findingown data

    CAF resulted in an increased serum glycerol concentration from 126 ± 8 to 154 ± 10 μmol/L at 60 min post-treatment compared with all other trials (P≤0.05).

    “CAF resulted in an increased serum glycerol concentration (from 126 6 8 to 154 6 10 mmol/L) at 60 min post-treatment ingestion compared with all other trials (P # 0.05).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    During CAF and RCOF trials, plasma caffeine concentrations increased and peaked at 33.1 ± 1.4 and 36.8 ± 1.5 μmol/L just prior to the OGTT (t=60 min), respectively.

    “Within the CAF and RCOF trials, plasma caffeine concentrations increased, reaching peak concentrations of 33.1 6 1.4 and 36.8 6 1.5 mmol/L just prior to the initiation of the OGTT (t 5 60 min), respectively.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    C-peptide responses did not differ between RCOF and DECAF, or between PL and DECAF (P>0.05).

    “The C peptide responses between RCOF and DECAF, or between PL and DECAF, did not differ (P .0.05).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    C-peptide AUC was higher with CAF than both PL and DECAF (P≤0.05).

    “AUC analysis revealed a higher C peptide response (P # 0.05) with CAF than both PL and DECAF (Table 1).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Blood lactate concentration was higher during RCOF (1.5 ± 0.2 mmol/L) than PL (1.1 ± 0.1 mmol/L) (P<0.05).

    “The only treatment effect was a higher blood lactate concentration during the RCOF trial (1.5 6 0.2 mmol/ L) compared with the PL trial (1.1 6 0.1 mmol/L) (P , 0.05)”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    RCOF, PL, and DECAF did not change serum FFA concentrations from baseline.

    “Following the ingestion the RCOF, PL, and DECAF treatments, the FFA concentrations remained unchanged from baseline values.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductreasoning

    The insulin sensitivity index (ISI) was calculated using an equation described by Matsuda and DeFronzo, using whole blood glucose and serum insulin, but only for comparison among treatments and not to comment on absolute values.

    “To get an estimate of whole body insulin sensitivity, the insulin sensitivity index (ISI) was calculated using an equation described by Matsuda and DeFronzo (22).”
    • Also stated in: § MATERIALS AND METHODS · plain
      “Although we do acknowledge that we have used whole blood glucose and serum insulin for the calculation, the use of this index was for comparison purposes among treatments only and not to comment on absolute values obtained.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [22] Matsuda, 1999, Insulin sensitivity indices obtained from oral glucose tolerance testing: Comparison with the euglycemic insulin clamp, Diabetes Care. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    If chronic RCOF ingestion attenuates the insulin-antagonistic effects of epinephrine while increasing exposure to insulin-sensitizing compounds, this may account for some or most of the reduction in risk for type 2 diabetes.

    “Taken together, if chronic RCOF ingestion results in the attenuation of the insulin-antagonistic effects of epinephrine while increasing exposure to insulin-sensitizing compounds, like chlorogenic acids and quinides, this may account for some, if not most, of the reduction in risk for the development of type 2 diabetes.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    DECAF resulted in either a lower intestinal glucose absorption or a higher glucose clearance.

    “Considering the fact that an identical amount of glucose was ingested in both the DECAF and PL trials, either DECAF resulted in a lower intestinal glucose absorption or a higher glucose clearance.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Consumption of ≥6 cups of coffee per day decreased the relative risk of developing type 2 diabetes in men and women by 54% and 29%, respectively.

    “Salazar-Martinez et al. (12) reported that the consumption of $6 cups of coffee per day decreased the relative risk of developing type 2 diabetes in both men and women by 54 and 29%, respectively.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [12] Salazar-Martinez, 2004, Coffee consumption and risk for type 2 diabetes mellitus, Ann Intern Med. source

      Not checked in the free run.

  • May combine two claims. The quote only partly states this claim.

    Interpretationown data

    The effects of CAF and RCOF on lipolysis differ, as CAF increased FFA and glycerol while RCOF did not, despite similar epinephrine elevations.

    “These findings not only provide further evidence that CAF and RCOF do not behave synonymously with respect to glucose metabolism but may also provide evidence that they have differential effects on other aspects of metabolism (i.e., lipolysis).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    On the day prior to each experiment, subjects refrained from performing any strenuous activity to maintain muscle glycogen stores.

    “On the day prior to each experiment, subjects refrained from performing any strenuous activity to maintain muscle glycogen stores.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Caffeine ingestion reduces whole body glucose disposal by 15-30%, predominantly at the level of skeletal muscle.

    “Similarly, studies employing the euglycemic-hyperinsulinemic clamp technique have confirmed that caffeine ingestion reduces whole body glucose disposal by 15-30% (9)(10)(11), predominantly at the level of the skeletal muscle (11).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites (9)(10)(11)

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    For a given subject, all experiments were conducted at the same time of day.

    “For a given subject, all experiments were conducted at the same time of day.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Chlorogenic and quinide compounds found in coffee are suggested to decrease glucose absorption and enhance nonskeletal muscle glucose disposal, respectively.

    “In terms of glucose metabolism, both the chlorogenic and quinide compounds found in coffee are suggested to decrease glucose absorption (16) and enhance nonskeletal muscle glucose disposal (17), respectively.”
    • Also stated in: § DISCUSSION · hedged
      “Recent evidence demonstrates that the chlorogenic acids and quinide compounds found in DECAF may delay intestinal glucose absorption (16) and does enhance nonmuscle glucose uptake (17), respectively.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [16] Johnston, 2003, Coffee acutely modifies gastrointestinal hormone secretion and glucose tolerance in humans: glycemic effects of chlorogenic acid and caffeine, Am J Clin Nutr. source

      Not checked in the free run.

    • cites [17] Shearer, 2003, Quinides of roasted coffee enhance insulin action in conscious rats, J Nutr. source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Epinephrine is a potent antagonist of insulin-mediated glucose disposal.

    “although epinephrine is a potent antagonist of insulin-mediated glucose disposal (31)(32)(33)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites (31)(32)(33)

      Not checked in the free run.

  • May combine two claims.

    Study design and conductown data

    Plasma caffeine concentrations were undetectable at baseline and did not differ among baseline periods, confirming compliance with pre-experimental dietary restrictions.

    “Plasma methylxanthine concentrations did not differ among the baseline periods and, in general, concentrations were undetectable, confirming compliance with pre-experimental dietary restrictions.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    For subjects who began experiments in the early afternoon, a small breakfast was permitted; its composition was recorded and an identical breakfast was consumed prior to each experiment.

    “Although most subjects (n ¼ 9) entered the laboratory after a 10-12-h overnight fast, for those who began their experiments in the early afternoon (n ¼ 2), a small breakfast was permitted.The composition of the breakfast was recorded and an identical breakfast was consumed prior to each experiment.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Compounds present in coffee may enhance glucose tolerance and may provide a partial explanation for the reported decrease in incidence of type 2 diabetes in chronic coffee users.

    “the different glucose response elicited by PL and DECAF further suggests that compounds present in coffee may enhance glucose tolerance and may provide a partial explanation for the reported decrease in incidence of type 2 diabetes in chronic coffee users.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Caffeine ingestion increases exercise performance time, whereas caffeinated coffee ingestion does not, despite similar caffeine concentrations.

    “Graham et al. (15) demonstrated that while caffeine ingestion resulted in an increase in exercise performance time, caffeinated coffee ingestion did not.This lack of a coffee effect occurred despite the fact that similar caffeine concentrations were obtained in both trials.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [15] Graham, 1998, Metabolic and exercise endurance effects of coffee and caffeine ingestion, J Appl Physiol. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    For technical reasons, epinephrine concentrations were measured for a subset of subjects (n=6).

    “For technical reasons, epinephrine concentrations were measured for a subset of subjects (n ¼ 6).”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductnone given

    Subjects abstained from caffeine-containing beverages/substances and alcohol and maintained regular activity patterns prior to experiments.

    “Also during this time subjects abstained from caffeine-containing beverages and/or substances and alcohol and maintained regular activity patterns.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    The present study demonstrated significant elevations in epinephrine concentrations during both CAF and RCOF trials; however, due to similar epinephrine concentrations among these treatments, it is unlikely that this can explain the attenuated effect observed on glucose tolerance with RCOF.

    “the present study did demonstrate significant elevations in epinephrine concentrations during both the CAF and RCOF trials; however, due to the fact that epinephrine concentrations were similar among these treatments, it is unlikely that this can explain the attenuated effect observed on glucose tolerance with RCOF.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    All subjects but one were noncaffeine users; the one caffeine user abstained from caffeine for 7 d prior to the first experiment and throughout the remainder of the study.

    “All subjects but one were considered noncaffeine users as defined by the consumption of #2 caffeinated coffee or tea beverages and/or #5 caffeine-containing soft drinks per week.The one subject considered a caffeine user abstained from caffeine for 7 d prior to the first experiment and throughout the remainder of the study.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    The study was conducted as four double-blinded, randomized trials in 11 healthy males.

    “Eleven healthy males underwent 4 double-blinded randomized trials.”
    • Also stated in: § MATERIALS AND METHODS · plain
      “All subjects completed 4 trials in a double-blinded, randomized fashion, separated by 1-2 wk.”
    Quote in the paperNot a substantial claim
28 of 28

  • The paper relies on this without support.

    The study is the first to directly compare the effects of CAF and RCOF ingestion on glucose metabolism within a single study.

    “This study is the first that we know of to directly compare the effects of CAF and RCOF ingestion on glucose metabolism within a single study.”
1 of 1

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • In another similar study, vegetarians had significantly lower average CRP (0.72 mg/l) than non-vegetarians (1.62 mg/l).

    “Another study with a similar design comparing vegetarians with non-vegetarians also found that the average CRP concentration was significantly lower in the vegetarian group (0•72 v. 1•62 mg/l) (294) .”

    From Dietary factors and low-grade inflammation in relation to overweight and obesity (2011) · cites this paper as [294]

  • Vegetarian dietary patterns are associated with lower concentrations of chronic low-grade inflammation and endothelial function markers than non-vegetarian diets.

    “Dietary patterns consistent with vegetarianism were associated with lower concentrations of markers of chronic low-grade inflammation and endothelial function when compared with non-vegetarian diets (294 -296) .”

    From Dietary factors and low-grade inflammation in relation to overweight and obesity (2011) · cites this paper as [294]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • CAF-DECAF insulin sensitivity comparison is reversed

    Minor

    The text says ISI was higher with CAF than DECAF, but Table 1 reports 7.6 for CAF and 9.0 for DECAF. The discussion repeats the reversed comparison.

  • Other ISI comparisons contradict Table 1 significance labels

    Minor

    The text says no other treatments differed in ISI, but Table 1 assigns CAF the label "a" and both PL and RCOF the label "b"; its caption says means without a common letter differ at P ≤ 0.05.

2 of 2

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Related

Authors
Battram, D. S., Arthur, R., Weekes, A., & Graham, T. E.
Affiliations
University of Guelph (CA)
Corresponding author
Battram, Danielle S
ORCID
Arthur, Rebecca
Venue
The Journal of Nutrition
Publisher
Elsevier BV
Published
2006-05
Volume
136
Issue
5
Pages
1276-1280
ISSN
0022-3166 (ISSN-L)
DOI
10.1093/jn/136.5.1276
OpenAlex
W2100044362
Cited by
135
References
37
Citations by year
2025: 3 · 2024: 1 · 2023: 3 · 2021: 6 · 2020: 5 · 2019: 5 · 2018: 7 · 2017: 3 · 2016: 5 · 2015: 10 · 2014: 8 · 2013: 10 · 2012: 10
FWCI
7.32
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Nutrition (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Pharmacology › Coffee research and impacts
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Keywords
caffeine, coffee, glucose tolerance, impaired glucose tolerance, decaffeinated coffee, type 2 diabetes, insulin response, oral glucose tolerance test
MeSH terms
Alkaloids, Blood Glucose, C-Peptide, Caffeine, Coffee, Epinephrine, Fatty Acids, Nonesterified, Humans, Insulin, Kinetics, Male, Xanthines, Glucose Intolerance

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