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Study Title and Description

Fourteen well-described caffeine withdrawal symptoms factor into three clusters.



Key Questions Addressed
1 For [population], is caffeine intake above [exposure dose], compared to intakes [exposure dose] or less, associated with adverse effects on behavior*?
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Primary Publication Information
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TitleData
Title Fourteen well-described caffeine withdrawal symptoms factor into three clusters.
Author S Ozsungur,D Brenner,A El-Sohemy,
Country
Year 2009
Numbers

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Extraction Form: Behavior - Design Details - INCLUDED Studies
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Design Details
Question... Follow Up Answer Follow-up Answer
Refid 18795265
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What outcome is being evaluated in this paper? Behavior
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What is the objective of the study (as reported by the authors)? The aim of the present study was to use a principal components method of factor analysis to determine if the 14 well-characterized caffeine withdrawal symptoms co-present in factors and to investigate whether the likelihood of reporting the factors of symptoms is associated with habitual intake levels of caffeine.
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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) Study population and data collection Men (n=253) and women (n=589) aged 20–29 years were recruited by advertisement from the University of Toronto campus to participate in the Toronto Nutrigenomics and Health Study. Pregnant or nursing females were excluded from the study. Anthropometric measurements were taken, and a general health and lifestyle questionnaire was used to provide information on medical history, use of medication, cigarette smoking, and physical activity. Caffeine intake assessment Caffeine intake was assessed using a semi-quantitative food frequency questionnaire (FFQ), which is a method that has been shown to be a valid and reliable approach to capture average daily caffeine intake (Kabagambe et al. 2001). The FFQ assessed dietary intake over the past month and included questions related to the consumption of caffeinated coffee, tea, cola, and other caffeinated soda beverages, chocolate, and "energy drinks." The standard portion size for caffeinated tea, coffee, and energy drink beverages in the FFQ was fixed as 1 cup equivalent to 8 oz. The standard portion size for cola and other soda beverages was fixed as 1 can/glass/bottle equivalent to 12 oz. In order to help subjects report their beverage portion sizes more accurately, three portion cup sizes of 8, 12, and 16 oz were presented to them as examples. Subjects were asked to select one of ten categories of caffeinated beverage intake: never, 1 cup/ week or less, 2 to 4 cups/week, 5 to 6 cups/week, 1 cup/ day, 2 cups/day, 3 cups/day, 4 cups/day, 5 cups/day, or 6 or more cups/day. Daily caffeine intake levels derived from the FFQ were calculated using the US Department of Agriculture food composition data file (USDA 2007). Subjects were asked if they ever and how often they purchased and consumed coffee outside of the home or workplace. Subjects were also asked to indicate their usual method of preparing coffee at home or work. Caffeine intake values from coffee consumption were determined after taking into account the variable caffeine content and the frequency of the usual brand of coffee purchased outside of the home or workplace, as well as the caffeine content of coffee according to the usual method of preparation (Cornelis and El-Sohemy 2007). The caffeine intake values were then used to calculate the daily intake of caffeine in milligrams per kilogram body weight (bw) to provide two different measures of daily caffeine exposure as previously described (Barone and Roberts 1996). Caffeine intake from over-the-counter medications was determined using the general health and lifestyle questionnaire. Statistical analysis Population characteristics were assessed for the 495 subjects remaining after exclusions between three different categories of habitual caffeine intake. The cut points for the three categories of intake were 100 and 200 mg/day, which are equivalent to approximately 1 and 2 cups of coffee per day, respectively. The reported severities of the caffeine withdrawal symptoms were dichotomized into "no" (none) and "yes" (mild, moderate, and severe) because of the relatively low number of subjects reporting moderate or severe symptoms, which may reflect the relatively low average habitual caffeine consumption level (168.1 mg/day) in this population of young adults. We conducted a principal components analysis method of factor analysis using the outcome measures yes or no for each withdrawal symptom to identify any underlying connection within the data (Kim and Mueller 1978). The number of factors for the withdrawal symptoms was determined using a scree test as well as the Kaiser criterion for eigenvalues, as only those factors with values above 1 indicate that the variance explained by the factor is greater than any one input variable (Kaiser 1958). Factor structure was simplified by using orthogonal rotation to maximize the variance of the squared loadings for each factor. Items with factor loadings >0.50 were considered as a distinct symptom of that factor. Factor strength and the level of correlation between the items considered to be part of a factor were measured using Cronbach’s α coefficients. Subjects reporting a history of mood disorder were excluded from analyses on the "dysphoric mood" factor (n=75). Unconditional multivariate logistic regression models were adjusted for covariates and used to calculate odds ratios (OR) and 95% confidence intervals (CI). This was done in order to determine the likelihood of reporting a factor of withdrawal symptoms with increasing categories of caffeine consumption. Models were adjusted for age, sex, cigarette smoking (current vs. past or never), history of mood disorder (anxiety or depression), use of oral contraceptives (among women only), physical activity, and body mass index (BMI); however, only covariates that materially altered the effect estimates were included in the final adjusted models. Tests for multiplicative interactions between habitual caffeine intake and covariates on the outcome variables were conducted using Wald statistics. All statistical analyses were two-sided, and P values <0.05 were considered statistically significant. All data were analyzed using the Statistical Analysis Systems software (SAS V9.1; SAS Institute, Cary, NC, USA).
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How many outcome-specific endpoints are evaluated? 1
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What is the (or one of the) endpoint(s) evaluated? (Each endpoint listed separately) headache
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List additional health endpoints (separately).
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List additional health endpoints (separately)
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Notes measured as 14 symptoms and grouped into three clusters "fatigue and headache", "dysphoric mood", and "flu-like somatic"
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Clinical Clinical
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Physiological Physiological
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Other
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What is the study design? Cohort
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Randomized or Non-Randomized?
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What were the diagnostics or methods used to measure the outcome? Subjective
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Optional: Name of Method or short description Caffeine habits questionnaire Subjects were asked "Do you currently, or have you ever, consumed caffeine-containing beverages (e.g., coffee, tea, cola) regularly?" and chose one of three responses: (1) "Yes, I currently consume them regularly", (2) "Yes, I used to consume them regularly but do not anymore", or (3) "No, I have never regularly consumed them". Subjects were informed that "regularly" should be considered as daily or several days per week. Subjects were then asked "If yes, please indicate next to each of the following withdrawal symptoms the degree to which you experience(d) them up to 48 hours after ceasing to consume caffeine-containing beverages", and chose one of five responses for each of the 14 caffeine withdrawal symptoms: (1) "do not know", (2) "none", (3) "mild", (4) "moderate", or (5) "severe". Subjects were also given the option to select do not know if they had never abstained from caffeine, do not recall abstaining from caffeine, or do not know if they ever experienced a particular symptom. Subjects who responded "No, I have never regularly consumed them" to the question "Do you currently, or have you ever, consumed caffeine-containing beverages (e.g., coffee, tea, cola) regularly?" (n=245) were excluded from all analyses, since they were instructed to skip the caffeine withdrawal symptoms questions in the questionnaire. Subjects who responded "Yes, I used to consume them regularly but do not anymore" (n=102) were also excluded from all analyses, since some of these subject may have been dealing with long-term retrospective memory and may have had difficulty recalling their caffeine withdrawal symptoms
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Caffeine (general) Caffeine (general)
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Coffee
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Chocolate
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Energy drinks
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Gum
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Medicine/Supplement
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Soda
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Tea
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Measured
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Self-report Self-report
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Children
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Adolescents
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Adults Adults
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Pregnant Women
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What was the reference, comparison, or control group(s)? (e.g. high vs low consumption, number of cups, etc.) high vs low consumption broken into groups (< 100 mg/day, 100-200 mg/day, > 200 mg/day)
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What were the listed confounders or modifying factors as stated by the authors? (e.g. multi-variable components of models.  Copy from methods) Models were adjusted for age, sex, cigarette smoking (current vs. past or never), history of mood disorder (anxiety or depression), use of oral contraceptives (among women only), physical activity, and body mass index (BMI); however, only covariates that materially altered the effect estimates were included in the final adjusted models. Tests for multiplicative interactions between habitual caffeine intake and covariates on the outcome variables were conducted using Wald statistics
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Provide a general description of results (as reported by the authors). Compared to <100 mg/day, the adjusted ORs (95% CI) for reporting the fatigue and headache factor with a habitual intake of 100–200 and >200 mg/day were 1.97 (1.21, 3.21) and 4.44 (2.50, 7.86), respectively. After excluding subjects who reported a history of mood disorder, the adjusted ORs (95% CI) for reporting the dysphoric mood factor with a habitual intake of 100–200 and >200 mg/day, compared to <100 mg/day, were 1.55 (0.96, 2.52) and 3.34 (1.99, 5.60), respectively. The likelihood of reporting the flu-like somatic factor did not increase with increasing habitual caffeine intake. The corresponding ORs (95% CI) for the flu-like somatic factor were 1.05 (0.52, 2.14) and 0.84 (0.40, 1.77).
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Did the authors perform a dose-response analysis (or trend/related analysis)? No
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What were the authors's observations re: trend analysis?
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What were the author's conclusions? In summary, 14 well-described caffeine withdrawal symptoms factored into three clusters of caffeine withdrawal symptoms that we termed fatigue and headache, dysphoric mood, and flu-like somatic. The three factors may represent different underlying mechanisms of caffeine withdrawal. Increasing caffeine intake was associated with an increase in the likelihood of reporting symptoms of the fatigue and headache and dysphoric mood factor, but not the flu-like somatic symptoms.
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What were the sources of funding? This work was supported by the Advanced Foods and Materials Network (AFMNet).
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What conflicts of interest were reported? The authors report no conflicts of interest.
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Does the exposure (dose) need to be standardized to the SR? No
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Provide calculations/conversions for the exposure based on the decision tree in the guide (for all endpoints/exposure levels of interest).
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List all the endpoint(s) followed by the dose (mg) which will be used in comparison to Nawrot.  Characterize value as LOAEL/NOAEL, etc. if possible.  headache - LOAEL = 100-200 mg caffeine/day tired - LOAEL = 100-200 mg caffeine/day
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Notes regarding selection/listing of endpoints and exposures/doses to be compared to Nawrot. The most sensitive of the three groups of symptoms was the 'fatigue and headache' factor which was significant at the 100-200 mg/day level OR=1.97 (1.21, 3.21). The dysphoric mood factor was significant at the > 200 mg/day level OR= 3.34 (1.99, 5.60). The flu-factor did not significantly increase.
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What is the importance of the study with respect to the adverseness of the outcome? Important
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