Advanced Search

Study Preview



Study Title and Description

Contribution of caffeine to the homocysteine-raising effect of coffee: a randomized controlled trial in humans.



Key Questions Addressed
1 For [population], is caffeine intake above [exposure dose], compared to intakes [exposure dose] or less, associated with adverse effects on cardiovascular outcomes?
  • Comments Comments (
    0
    ) |

Primary Publication Information
  • Comments Comments (
    0
    ) |
TitleData
Title Contribution of caffeine to the homocysteine-raising effect of coffee: a randomized controlled trial in humans.
Author P Verhoef,WJ Pasman,T Van Vliet,R Urgert,MB Katan,
Country
Year 2002
Numbers

Secondary Publication Information
There are currently no secondary publications defined for this study.


Extraction Form: Cardiovascular Design
Design Details
Question... Follow Up Answer Follow-up Answer
What outcome is being evaluated in this paper? Cardiovascular
  • Comments Comments (
    0
    ) |
What is the objective of the study (as reported by the authors)? In the present study we tested whether caffeine is responsible for the higher plasma concentrations of total homocysteine during consumption of paper-filtered coffee.
  • Comments Comments (
    0
    ) |
Provide a general description of the methods as reported by the authors. Information should be extracted based on relevance to the SR (i.e., caffeine related methods) Subjects and design The subjects were recruited from a pool of volunteers registered at the Institute. Subjects were eligible if they usually drank > 6 cups regular filtered or instant (soluble) coffee daily; were between 18 and 65 y of age; had a body mass index (in kg/m2) < 30; consumed < 28 alcohol-containing beverages per week if male and < 21 if female; had no history of cardiovascular or gastrointestinal disease; were healthy on the basis of a physical examination, blood tests, and dipstick urinalysis; were not consuming a prescribed diet; had not used vitamin B supplements within 3 mo before entering the study; and had a plasma total homocysteine concentration < 25 umol/L. We used a Latin-square design with 3 treatments given in random order for 2 wk each: caffeine (test treatment), paper-filtered coffee (positive control treatment), and placebo (negative control treatment). For caffeine and placebo treatment this was a double-blind study. Fifty-four volunteers were stratified by sex and fasting homocysteine concentration (measured at a screening visit, approx. 1 mo before the study) and were then randomly assigned to 1 of 6 treatment sequences. Caffeine treatment consisted of 6 capsules (each containing 145 mg caffeine) providing a total of 870 mg caffeine/d. Coffee consumption was not allowed. Coffee treatment consisted of 0.9 L coffee/d, brewed with 1 L water and 52 g ground coffee. While designing our study, we prepared coffee in this way and the total amount of caffeine provided by this brew was measured to be approx. 870 mg. Placebo treatment consisted of daily consumption of 6 capsules, each containing 145 mg cellulose (Avicel; Fagron, Nieuwerkerk aan den Yssel, Netherlands). The procedures and restrictions were similar to those mentioned above. All treatment periods consisted of 3 d of gradual withdrawal from the previous treatment and, simultaneously, gradual habituation to the next treatment, followed by 11 d of the next treatment. The participants starting with the paper-filtered coffee did not have a habituation period: they maintained their habitual coffee consumption for the first 3 d and started coffee treatment on day 4. Caffeine-containing products (chocolate, chocolate drinks, cola, tea, and certain painkillers) were prohibited during the entire trial. The subjects were asked not to change their usual dietary habits during the trial. During the study, 6 subjects dropped out: 2 because of severe headaches, 1 because of study-related illness, 1 for personal reasons, and 2 for unknown reasons. Thus, 48 subjects completed the trial. Supply of Study Substances and Coffee Preparation Subjects received an electric-drip filter coffee maker, paper filters, a 0.7-L insulated container, and portions of 26 g finely ground coffee. Twice per day, the subjects prepared approx. 0.45 L coffee with 0.5 L water and 26 g ground coffee. About 0.05 L was retained in the filter during each coffee preparation. We used Douwe Egberts Roodmerk brand (Sara Lee/DE, Utrecht, Netherlands) coffee—a blend of arabica and robusta beans widely used the Netherlands. The capsules were provided in 4 medication-dispenser boxes, each of which contained enough capsules for 4 d. In addition to each treatment, the subjects were provided with packages of rbal tea, which contained herbs and spices such as mint, fennel seed, and licorice. At the last visit of each treatment period, the remaining portions of coffee and capsules were returned and counted. Blood Sampling and Assays Both fasting and nonfasting venous blood samples were collected on days 11 and 14 of each treatment period. After blood collection between 0800 and 0930 (ie, after the subjects had been fasting for ≥ 12 h), the subjects consumed a standard breakfast consisting of 2 slices of whole-meal bread with low-fat margarine (one with jam and one with colored sugar sprinkles), a glass of orange juice, and one-sixth of the daily treatment (ie, 1 cup coffee or 1 capsule taken with 1 cup water). The subjects were then free to leave the institute but had to return 4 h later for a second blood collection (between 1200 and 1330). In the meantime, the subjects had to consume a snack (ie, a shortbread biscuit) that we provided and another 2 cups coffee (ie, they finished the 0.45 L coffee that had been prepared) or 2 cups water with 2 capsules. The subjects were not allowed to eat or drink anything else except tap water. The fasting blood samples were used for homocysteine and B vitamin analyses, and the nonfasting blood samples were used for homocysteine and caffeine analyses. Caffeine concentrations were used to check compliance. Total homocysteine was measured by HPLC. Statistics Treatment effects were studied first with analysis of variance (ANOVA). If the ANOVA indicated an overall treatment effect (P ≤ 0.05), the treatment means were compared with one-sided, paired t tests. For each subject, the values obtained on days 11 and 14 of each treatment were averaged. The responses were calculated by subtracting the subject’s average value at the end of the placebo treatment from that at the end of the caffeine or coffee treatment. The aim of our study was to test the hypothesis that caffeine is responsible for the homocysteine-raising effect of coffee, ie, 1) coffee raises homocysteine, 2) caffeine raises homocysteine, and 3) the effect of caffeine is equal to that of coffee. Statement 1 is a logical consequence of statements 2 and 3; therefore, statement 1 is redundant. Hence, statement 1 was dropped and we were left with 2 comparisons for which a Bonferroni correction should be made, ie, dividing the significance level alpha by 2. We tested one-sided because our hypothesis was that caffeine would either raise homocysteine or fail to affect it; we considered it unlikely, a priori, that caffeine would lower homocysteine. We therefore used alpha = 0.05 (ie, 0.10 divided by 2). Setting the alpha level to < 0.05 could introduce a type 2 error, ie, a false-negative conclusion. Carryover effects were tested for and found to be absent. Subject characteristics and serum concentrations of caffeine are presented descriptively. SAS software (version 6.12; SAS Institute Inc, Cary, NC) was used.
  • Comments Comments (
    0
    ) |
How many outcome-specific endpoints are evaluated? 1
  • Comments Comments (
    0
    ) |
What is the (or one of the) endpoint(s) evaluated? (Each endpoint listed separately) Plasma total homocysteine
  • Comments Comments (
    0
    ) |
List additional health endpoints (separately). 2
  • Comments Comments (
    0
    ) |
List additional health endpoints (separately).3
  • Comments Comments (
    0
    ) |
List additional health endpoints (separately).4
  • Comments Comments (
    0
    ) |
List additional health endpoints (separately).5
  • Comments Comments (
    0
    ) |
List additional health endpoints (separately).6
  • Comments Comments (
    0
    ) |
Clinical, physiological, other Physiological
  • Comments Comments (
    0
    ) |
What is the study design? Controlled Trial
  • Comments Comments (
    0
    ) |
Randomized or Non-Randomized? RCT
  • Comments Comments (
    0
    ) |
What were the diagnostics or methods used to measure the outcome? Objective
  • Comments Comments (
    0
    ) |
Optional: Name of Method or short description Total homocysteine was measured by HPLC.
  • Comments Comments (
    0
    ) |
Caffeine (general) Caffeine (general)
  • Comments Comments (
    0
    ) |
Coffee, Chocolate, energy drink, gum, medicine/supplement, soda, tea, other? Coffee
  • Comments Comments (
    0
    ) |
Measured or self reported? Measured
  • Comments Comments (
    0
    ) |
Children, adolescents, adults, or pregnant included? Adults
  • Comments Comments (
    0
    ) |
What was the reference, comparison, or control group(s)? (e.g. high vs low consumption, number of cups, etc.) Subjects served as their own controls
  • Comments Comments (
    0
    ) |
What were the listed confounders or modifying factors as stated by the authors? (e.g. multi-variable components of models.  Copy from methods) None
  • Comments Comments (
    0
    ) |
What conflicts of interest were reported? No information provided
  • Comments Comments (
    0
    ) |
Refid 12450889
  • Comments Comments (
    0
    ) |
What were the sources of funding? Supported by the Wageningen Centre for Food Sciences, an alliance of major Dutch food industries; TNO Nutrition and Food Research; and Wageningen University and Research Centre, with financial support from the Dutch government.
  • Comments Comments (
    0
    ) |




Results & Comparisons

No Results found.