CAFEINE CAS : 58-08-2 - UNEP Chemicals

OECD SIDS CAFFEINE
Case reports and clinical studies of caffeine withdrawal most frequently reported symptoms of abrupt
withdrawal as mild to moderate headache beginning 12-24 hours after terminating intake (300 mg/day) and
lasting up to a week (Griffiths and Mumford, 1995, Griffiths and Woodson, 1988, Evans and
Griffiths, 1992). Decreased responsiveness to daily caffeine (500 mg/day) administration with respect to
blood pressure (Ammon et al., 1983, Roberston et al., 1981), diuresis (minimal effectiv diuretic dose
70 mg/day) (Eddy and Downs, 1928), and plasma epinephrine, norepinephrine, and plasma renin
activity (250 mg/day) (Robertson et al., 1978), but not to the effect of caffeine on urinary calcium
excretion (300 mg/day) was reported (Massey and Opryszek, 1990). No effect on mood and alertness
was seen after single caffeine dose (600 mg/day) (Sicard et al., 1996) or withdrawal (300 mg/day)
(Comer et al., 1997). Other studies on caffeine deprivation found an association with decreased vigor
and performance on reaction and increased fatigue (250 mg/day) (Phillips-Bute and Lane, 1998,
Bernstein et al., 1998).
3.1.1.4 Carcinogenicity
Heavy coffee consumption tends to be associated with other risk factors for various types of cancer, e.g.
smoking, alcohol, physical inactivity (Giovannucci, 1998). Residual confounding might explain weak
positive associations between caffeine consumption and lung, bladder, or pancreas cancer.
Based on the currently available literature Nehlig and Debry’s (1996) conclusion that in the doses
usually consumed by man, coffee does not have any potential carcinogenic effect can still be supported.
Whether the consumption of doses higher than 4 mg/kg/day slightly enhances or lowers the risk for some
cancer types is currently not clear.
The IARC evaluates the carcinogenicity in humans of caffeine as inadequate evidence (IARC 1991).
3.1.1.4.1 Different sites
The effect of caffeine consumption (av. 317 mg/day) on mortality was evaluated in a historical cohort study
of 10,064 diagnosed hypertensive individuals participating in the Hypertension Detection and Follow-up
Program from 1973 to 1979. No evidence was found for an association between increased level of
caffeine consumption (up to > 428 mg/day) and increased cancer mortality during the following four years
(Martin et al., 1988).
3.1.1.4.2 Breast
Several case-control studies provided no association between coffee intake (up to ≥ 7 cups/day) and
breast cancer risk (IARC, 1991). Also new case-control studies confirmed this result (Hunter, 1992,
McLaughlin et al., 1992, Folsom et al., 1993, Levi et al., 1993, Smith et al., 1994, Tavani et al.,
1998).
3.1.1.4.3 Colon
Cohort studies that addressed the issue of coffee drinking (up to ≥3 cups/day) and risk of cancer of the
colon have generally been interpreted as showing no association. There are case-control studies that
indicated inverse associations and others find a risk. Bias and confounding could not be excluded as the
source of the apparent associations (IARC, 1991). In recent case-control and cohort studies no increased
risk of colorectal cancer from caffeine intake (up to ≥7 cups/day) was found (Cipriani and Geddes,
1996, Giovannucci, 1998, Hartman et al., 1998, Tavani et al., 1997). The lower risk of colorectal
cancer with high vs. low coffee consumption as determined in the meta-analysis by Giovannucci (1998)
might be due to an avoidance of coffee by unidentified high-risk individuals, or due to enhanced colonic
motility induced by coffee, or due to antimutagenic components in coffee (not necessarily caffeine).
3.1.1.4.4 Bladder
UNEP PUBLICATIONS 17