Vol.2, No.9, 997-1001 (2010) Health
Copyright © 2010 SciRes. Openly accessible at http://www.scirp.org/journal/HEALTH/
Effects of cola intake on fertility: a review
Atsushi Imai1*, Satoshi Ichigo2, Hiroshi Takagi2, Kazutoshi Matsunami2, Noriko Suzuki3,
Akio Yamamoto3
1Institute of Endocrine-Related Cancer, Matsunami General Hospital, Gifu, Japan;
*Corresponding Author: aimai@matsunami-hsp.or.jp
2Department of Obstetrics and Gynecology, Matsunami General Hospital, Gifu, Japan
3Department of Obstetrics and Gynecology, Gifu University School of Medicine, Gifu, Japan
Received 22 June 2010; revised 12 July 2010; accepted 14 July 2010.
The consumption of soft drinks has increased
considerably during the last decades. Among
them, the cola-based preparations are possibly
the refreshments with the largest sales world-
wide. During the previous years, important
concerns have been raised about the effects of
colas on human health. In this review, we in-
troduce the cola effects on reproduction in-
cluding pregnancy miscarriages, ovulatory and
menstrual disorders, and reduced semen quality.
Although caffeine intoxication may be thought
to play the most important role, a component of
cola other than caffeine, or in combination with
caffeine, may be associated with increased risk
of reproductive hazards in heavy cola (> 1 L per
day)-consumers. Cola discontinuation usually
leads to an uneventful recovery in the most
cases suggesting justification of limitations in
the maximum recommended daily dose of these
soft drinks. Cola is not an essential beverage,
and abstaining from drinking more than 1 L per
day is a minor intrusion in one’s personal life.
Despite these uncertainties, this growing know-
ledge may alarm the fertility risk of chronic cola
intake in peoples of childbearing age.
Keywords: Cola; Soft Drink; Caffeine; Semen;
Miscarriage; Ovulation
The consumption of soft drinks has increased consider-
able during the last decades. Among them, the cola-
based preparations are possibly the refreshments with
the largest sale worldwide. During the previous years,
important concerns have been raised about the effects of
colas on human health. In addition to the possible detri-
mental effects of chronic cola consumption (enamel sof-
tening [1,2], bone demineralization [3,4], hypokalemic
myopathy [5-7], development of metabolic syndrome
and diabetes mellitus [8-10], and chronic kidney dis-
eases [11,12]), several lines of evidence suggest that the
chronic consumption of large amounts of cola-based soft
drinks may increase the risk of reproductive problems
such as decreased fetal growth, preterm delivery, and
spontaneous abortion [13-16]. However, results from
these epidemiological studies suggesting the association
between cola consumption and such outcomes have been
conflicting and the available information is incomplete
and remains controversial. The observations may have
important public health implications as, recently, trends
of increasing the portion size of these preparations have
been noticed. With the aim of evaluating the available
epidemiological evidence of the effect of cola consump-
tion on reproductive quality (see Table 1), a systematic
qualitative review was conductive.
Cola contains many different chemical compounds and
no certainty exists as to which ones may be associated
with disease risk.
Cola soft drinks may contain large amounts of glucose
(up to 11 g of sugar/dL) and high-fructose corn syrup.
Highly caloric carbonated soft drinks are often sweet-
ened with high fructose corn syrup, which makes soda
inexpensive to produce. While sugary soda may be sold
cheaply as a food item and yield a profit, they provide
little satiety. Thus, the excessive consumption of theses
preparations may lead to glycemic load, resulting in os-
motic diuresis and hyperinsulinemia. Fructose itself may
cause kidney damage, perhaps mediated by uric acid
Cola contains sufficient amounts of caffeine ranging
A. Imai et al. / HEALTH 2 (2010) 997-1001
Copyright © 2010 SciRes. Openly accessible at http://www.scirp.org/journal/HEALTH/
Table 1. Main points of the cola (carbonated soft drink) - in-
duced reproductive hazards.
Outcomes Amount of cola
cause Refs.
Reduced sperm
count (30% below
the average in
> 1 L per day
during the past
in cola other
than caffeine
Ovulatory disor-
der infertility
> 2 soft drinks a
Contents in
cola other
than caffeine
or sugar
Shortened menses
duration and cycle
> 300 mg of
caffeine per day Caffeine [21]
Increased risk of
miscarriage (haz-
ard ratio of 2.23)
200 mg of caf-
feine per day
during pregnancy
Caffeine [45,50]
*Assumed caffeine content of 150 mg/L.
from 95 to 160 mg/L. Caffeine, 1,3,7-trimethylxanthine,
is among the most frequently ingested pharmacologi-
cally active substances [18,19]. Carbonated soft drinks
and coffee are the main sources of caffeine intake.
Other components in cola, such as phosphorus in dark
cola, may reveal significant physiological actions.
Women who consume caffeine may be less likely to
have long menses. This phenomena is biologically likely
plausible because caffeine is a known vasoconstrictor
[20], reducing uterine blood flow. Constriction of uterine
blood vessels would be expected to reduce uterine blood
flow, which could reduce menstrual bleeding and shorten
the duration of menses [21]. Caffeine may alter the dura-
tion of menstrual cycle via the effect of caffeine on sex
hormones or the hormone receptors [22]. However, the
results of studies of caffeinated beverage consumption in
relation to fecundity are inconsistent. Several studies in
humans have reported an association between caffeine
intake and delayed time to conception [23-26], in con-
trast, others have shown either no association [27,28] or
a relation only at very high levels of intake [29]. Most of
these studies have retrospectively collected information
on alcohol and caffeine intake, making the results sus-
ceptible to biases. The study by Fenster et al. [21] de-
scribed the relation between caffeine intake and men-
strual function was examined in 403 healthy premeno-
pausal women who belonged to Kaiser Permanente
Medical Care Program in 1990-1991. They collected
information about caffeinated beverage intake as well as
other lifestyle, demographic, occupational, and envi-
ronmental factors. Subjects collected daily urine samples
and completed a daily diary for an average of five men-
strual cycles. Caffeine intake was not strongly related to
an increased risk for anovulation, short luteal phase, long
follicular phase, long cycle, or measures of within-
woman cycle variability. Chavarro et al. [30] followed
18,555 married women without a history of infertility for
8 years as they attempted to become (or became) preg-
nant. Soft drinks were the only beverages positively re-
lated to ovulatory infertility. Intake of caffeinated soft
drinks was associated with a higher risk of ovulatory
disorder infertility among women consuming at least 2
or more soft drinks per day. Women consuming 2 or
more caffeinated soft drinks per day had a 47% greater
risk of ovulatory infertility than women who consumed
less than 1 caffeinated soft drink per week. Their analy-
ses suggested that neither caffeine nor fructose was re-
sponsible for this association. Extreme comparisons of
caffeine and coffee intake suggested no association or an
inverse association with ovulatory disorder infertility.
Some constituents in cola other than caffeine or sugar
may cause ovulatory disorder.
Regarding the risk of ovarian cancer developments,
laboratory data suggest that caffeine or some compo-
nents of coffee may cause DNA mutations and inhibit
tumor suppressor mechanisms, leading to neoplastic
growth. An increased risk was observed in the multi-
variate model for women who reported drinking five or
more cups/day of caffeinated coffee compared to women
who reported drinking none. Decaffeinated coffee, total
coffee, and caffeine were not statistically significantly
associated with ovarian cancer incidence. A component
of coffee other than caffeine, or in combination with
caffeine, may be associated with increased risk of ovar-
ian cancer in postmenopausal women who drink five or
more cups of coffee a day [31].
A recent Danish study revealed that sperm counts are
lower in men who drink cola of 1 L (estimated to contain
100-140 mg of caffeine) or more per day, averaging 31%
below the average in control [32,33]. This cola’s effect
on sperm seems not to be attributable to their caffeine
content; caffeine intake of < 800 mg per day and cola
consumption of < 14 0.5-L bottles per week is not asso-
ciated with reduced semen quality. The reduction in se-
men quality among high-quantity cola drinkers must be
attributed to constituents in cola other than caffeine be-
cause the caffeine content of cola is not high. They also
added that although the cola drinkers’ sperm count was
still within the normal range, at 35 million/mL, cola
might nonetheless dampen their fertility [33]. Among the
study participants, those not drinking cola had an aver-
A. Imai et al. / HEALTH 2 (2010) 997-1001
Copyright © 2010 SciRes. Openly accessible at http://www.scirp.org/journal/HEALTH/
age count of 50 million/mL.
In fact, previous studies on caffeine intake and sperm
quality have been contradictory [34-36]. Alternatively,
these associations may be attributed to the less healthy
lifestyle and diet of high-quantity consumers. Heavy
quantity consumers of cola or caffeine had an unhealth-
ier lifestyle, which has previously been associated with
poorer semen quality [37-40]. To the extent possible,
many researchers considered these factors in the analy-
ses, and they did not appear to explain the caffeine and
cola associations. High-quantity caffeine and cola con-
sumers also had a less healthy diet, and previous studies
have found reduced semen quality among men who
consumed few fruits and vegetables and had a low intake
of antioxidant and trace minerals [33]. Cola contains
sufficient amounts of many minerals including phosph-
High cola and caffeine consumption may be related to
in utero exposure to caffeine. Ramlau-Hansen et al. [41]
studied the association between prenatal coffee and cur-
rent caffeine exposure and semen quality. There is a
tendency toward decreasing crude median semen volume
and adjusted mean testosterone and inhibin concentra-
tions with increasing maternal coffee consumption dur-
ing pregnancy. Sons of mothers drinking 4-7 cups/day
had lower testosterone levels than sons of mothers
drinking 0-3 cups/day. However caffeine intake had no
impact on semen quality.
Caffeine can readily cross the placental barrier to the
fetus [42]; its clearance is prolonged in pregnant women,
and its metabolism rate is low in the fetus because of
low levels of enzymes [43,44]. It may also influence cell
development through increasing cellular cyclic adeno-
sine monophosphate (cAMP) concentrations and de-
crease intervillous placental blood flow via increasing
circulating catecholamines [18,19,45]. Caffeine intake
during pregnancy has been suggested as a risk factor for
adverse reproductive outcomes. Therefore, caffeine could
have an adverse effect on fetal development. Indeed,
caffeine intake has been reported to increase the risk of
miscarriage [15,16,46-48]. Although numerous studies
on maternal caffeine consumption and the risk of mis-
carriage have been published since the 1980s, the effect
of caffeine intake on the risk of miscarriage remains
controversial because of methodological limitations in
past studies. Many studies have relied on retrospective
information, which is subject to recall bias [15,16,46-48].
Some had only a small number of participants, which
limited their power to detect an effect. Some did not take
into account potential confounding factors such as smok-
ing, alcohol consumption, and most importantly, preg-
nancy-related symptoms including nausea and vomiting.
Some recruited women who sought prenatal care at their
13th to 28th weeks of gestation, therefore too late in
pregnancy to study miscarriage. Such controversy has
led to the uncertainty about the health effects of caffeine
consumption during pregnancy among both clinicians
and pregnant women alike.
Weng et al. [45] demonstrated, in their prospective
cohort study, an elevated risk of miscarriage associated
with caffeine consumption during pregnancy and a dose-
response relationship with most of the risk associated
with caffeine consumption at 200 mg (which approxi-
mately 1.5 L cola contains) or greater per day. This ob-
served effect was independent of many potential con-
founders including pregnancy related symptoms such as
nausea, vomiting, and aversion to caffeine consumption.
Even among women who never changed caffeine con-
sumption pattern during pregnancy, there was an almost
80% increased risk of miscarriage associated with caf-
feine consumption of 200 mg/day or greater, although it
was not statistically significant because of reduced sam-
ple size by stratification. The increased risk of miscar-
riage appeared to be due to caffeine itself rather than
other possible chemicals in coffee because caffeine in-
take from noncoffee sources showed the similarly in-
creased risk of miscarriage. On the other hand, a similar
cohort study, published same month, by Svavitz et al.
[49] demonstrated that this can result in recall bias gen-
erating a positive results, whereas when caffeine expo-
sure is ascertained before miscarriage, the findings indi-
cate no effect of caffeine. To data, the literature is still
inconclusive regarding the influence of caffeine on mis-
carriage and the available information is incomplete and
remains controversial [47,50].
Although much epidemiological work has been con-
ducted, results from studies investigating the association
between cola consumption and outcomes such as repro-
ductive hazards have been conflicting and the available
information was incomplete and remained controversial.
As summarized in Table 1, our reviewing recent reports
suggest the association between cola consumption and
increased risk of reproductive hazards. In addition to
caffeine, cola contains a number of other chemical com-
pounds, and one or more of these could be physiologi-
cally active. Further studies might attempt to disentangle
a caffeine effect from a noncaffeine effect by comparing
different types of beverage drinkers. Cola is not an es-
sential beverage, and abstaining from drinking more than
1 L per day is a minor intrusion in one’s personal life.
A. Imai et al. / HEALTH 2 (2010) 997-1001
Copyright © 2010 SciRes. Openly accessible at http://www.scirp.org/journal/HEALTH/
The growing knowledge may alarm the fertility risk of
chronic cola intake in peoples of childbearing age.
Authors contributions: All authors discussed and
wrote the draft of the manuscript, and A.I. coordinated
the project and wrote the final version.
Conflict of interest statement: The authors report no
conflicts of interest.
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