An Overview of The Relationship Between Fertility and Caffeine Intake

Abstract

Caffeine is a psychoactive component with a chemical composition of
1,3,7-trimethylxanthine. Coffee, tea, energy drink, and chocolate are the
main sources of caffeine. There are several positive health effects of caffeine
on diabetes, Parkinson’s disease, and cardiovascular disease. However, the
relationship between caffeine consumption and reproductive health is
controversial. The aim of the present study was to determine the effects of
caffeine consumption on fertility. A literature search was conducted using
the electronic databases PubMed, Web of Science, Cochrane, and LILACS
with the search terms “fertility,” “infertility,” “fecundability,” “reproductive,”
“caffeine,” “coffee,” “tea,” and “caffeinated.” An additional manual search was
also performed for missing articles. At the end of the search, a total of 13
studies were included in the present study. Six studies reported negative
and two studies reported positive effects of caffeine on fertility by several
mechanisms such as affecting sex hormones and reducing clearance
during the luteal phase. However, no association was found between caffeine
and fertility or fecundability in five studies. According to study results
that revealed negative effects of caffeine, it may be recommended to males
and females who are planning to conceive to decrease caffeine intake, especially
from coffee. It may also be recommended to consume other types
of healthy beverages and foods without caffeine.

Full text

An Overview of The Relationship Between Fertility and Caeine Intake
Fertilite ve Kafein Alımı Arasındaki İlişkinin Değerlendirilmesi
Melahat Sedanur Macit, Yasemin Akdevelioğlu
Deparment of Nutrition and Dietetics, Gazi University, Ankara, Turkey
Correspondence Author/ Sorumlu Yazar: Melahat Sedanur Macit E-mail/E-posta: sedanur.macit@gmail.com
Received/Geliş Tarihi: 21.08.2017 Accepted/Kabul Tarihi: 12.11.2017 DOI: 10.5152/clinexphealthsci.2017.663
©Copyright by 2018 Journal of Marmara University Institute of Health Sciences - Available online at www.clinexphealthsci.com
©Telif Hakkı 2018 Marmara Üniversitesi Sağlık Bilimleri Enstitüsü - Makale metnine www.clinexphealthsci.com web sayfasından ulaşılabilir
INTRODUCTION
Caeine is one of the most common psychoactive components. Its chemical composition is 1,3,7-trimethylxanthine, which is found in
more than 60 plants and also produced in the industry (1). After entering the body, caeine is easily distributed in the body and exists in
the saliva, breast milk, embryo, and neonate owing to its ability to pass all membranes including the placental barrier (2,3). Caeine is a
component present in a large range of food such as coees, teas, chocolates, cocoa products, and soft and energy drinks. However, coee
is its main source (4). Table 1 shows the amount of caeine in these main sources.
Caeine is associated with several positive health eects for cardiovascular diseases, diabetes, and Parkinson’s disease (7). It is an ad-
enosine receptor antagonist and may also have several eects on reproductive health (8). Adenosine has eects on sperm capacity
via tyrosine phosphorylation with N6-cyclopentyladenosine (9). For the rst time, the Food and Drug Administration advised pregnant
women to decrease caeine intake (10). It was also recommended that pregnant women should not exceed 200 mg/day caeine intake.
Caeine is presented as one of the nutrients that have eects on dysmenorrhea and premenstrual syndrome (11). In addition, it is re-
ported to decrease fertility (12). The relationship between caeine and fertility was rst reported by Wilcox et al. in a prospective study.
According to their study results, per cycle probability of conceiving was decreased by 50% due to drinking one cup of coee. However,
study results are controversial owing to its designs, methodological failings, and call of bias. Caeine intake, below the recommend-
Abstract
Caeine is a psychoactive component with a chemical composition of
1,3,7-trimethylxanthine. Coee, tea, energy drink, and chocolate are the
main sources of caeine. There are several positive health eects of caeine
on diabetes, Parkinson’s disease, and cardiovascular disease. However, the
relationship between caeine consumption and reproductive health is
controversial. The aim of the present study was to determine the eects of
caeine consumption on fertility. A literature search was conducted using
the electronic databases PubMed, Web of Science, Cochrane, and LILACS
with the search terms “fertility,” “infertility,” “fecundability,” “reproductive,”
“caeine,” “coee,” “tea,” and “caeinated.” An additional manual search was
also performed for missing articles. At the end of the search, a total of 13
studies were included in the present study. Six studies reported negative
and two studies reported positive eects of caeine on fertility by sever-
al mechanisms such as aecting sex hormones and reducing clearance
during the luteal phase. However, no association was found between caf-
feine and fertility or fecundability in ve studies. According to study results
that revealed negative eects of caeine, it may be recommended to males
and females who are planning to conceive to decrease caeine intake, es-
pecially from coee. It may also be recommended to consume other types
of healthy beverages and foods without caeine.
Keywords: Caeine, coee, fertility, fecundability, pregnancy
Öz
Kafein 1,3,7-trimetilksantin kimyasal yapısında, biyoaktif bir bileşendir.
Kahve, çay, enerji içecekleri ve çikolata kafeinin ana kaynaklarıdır. Kafein
diyabet, Parkinson, kardiyovasküler hastalıklar gibi sağlık sorunları üzerine
olumlu etkileri vardır. Ancak kafeinin üreme sağlığına etkisi tartışmalıdır. Bu
derlemede kafein tüketiminin fertilite üzerine etkilerinin değerlendirilmesi
amaçlanmıştır. Pubmed, Web of Science, Cochrane, ve Lilacs elektronik veri
tabanlarında “fertilite”, “infertilite”, “üreme”, “kafein”, “kahve”, “çay”, “kafeinli”
terimleri ile tarama yapılmıştır. gözden kaçırılan çalışmaların olması ihti-
maline karşı ek olarak genel bir tarama yapılmıştır. tarama sonucu toplam
12 çalışma bu derlemeye dahil edilmiştir. Çalışmalardan 5’i kafeinin fertilite
üzerine olumsuz, 2’si olumlu etkileri olduğunu rapor etmektedir. Olumsuz
sonuçlar sunan çalışmalar genellikle kafeinin seks hormonlarına etkisi ve
lüteal fazı kısaltıcı etkilerine yoğunlaşmıştır. Ancak 5 çalışma kafein alımı ve
fertilite arasında herhangi bir ilişki bulmamıştır. Çalışma sonuçları doğrultu-
sunda gebelik planlayan çiftlere kafein alımını azaltmaları tavsiye edilebilir.
Ayrıca bireyler kafeinsiz içecekleri tüketimleri konusunda teşvik edilmelidir.
Anahtar Kelimeler: Kafein, kahve, fertilite, doğurganlık, gebelik
Review /
Derleme
Cite this article as: Macit MS, Akdevelioğlu Y. An Overview of The Relationship Between Fertility and Caeine Intake. Clin Exp Health Sci 2018; 8: 138-45.
138

ed levels (<200–300 mg/day), appears to have no serious eects on
reproductive life. It is still advisable to avoid excessive caeine in-
take for women and men who plan to conceive. The recommended
amount for conception is 100–200 mg/day, which is dened as mild
consumption and equivalent to fewer than two cups of coee per
day (12).
This relationship has been explained by several mechanisms in stud-
ies:
- There is an inverse correlation between caeine and estradiol in
pregnant woman.
- There is a positive correlation between caeine and sex hor-
mone-binding globulin.
- Caeine may decrease prolactin levels and may inhibit ovula-
tion.
- Caeine may aect the transportation of conceptus (4,13–16).
It was stated that the eects of coee may be due to dierent com-
ponents rather than caeine (4). However, it is dicult to distinguish
the eects of coee and caeine due to high correlation in their in-
take (17).
Pregnancy is a natural process and aected by several factors. It is
important to eliminate the possible risk factors for a healthy con-
ception and pregnancy. In terms of nutrition, caeine is one of the
nutrients that is thought to inuence reproductive health. However,
study results are not clear owing to dierent study types and designs.
This review aimed to sum up these study results and to assess the
relationship between caeine intake and fertility, fecundability, and
conception time.
METHODS
A literature search was conducted using the electronic databases
PubMed, Web of Science, Cochrane, and LILACS. The search terms
“fertility,” “infertility,” “fecundability,” “reproductive,” “caeine,” “coee,”
“tea,” and “caeinated” were used. The search was performed through
appropriate methods and keywords by using “AND” and “OR.” An ad-
ditional manual search was also performed for missing articles, and
one article was added to the study. Three studies were excluded in
this review owing to no access to full text and abstract (18–20). Out-
comes were determined by birth, fertility, fecundability, fecundabil-
ity rate (FR), and spontaneous abortion. With this regard, this review
is restricted to human studies of caeine and its associated factors
and excluded fetal death, congenital malformations, and gestation-
al age/preterm birth. We have only included spontaneous abortion
outcome that appears after conception.
Articles were viewed according to the following inclusion and exclu-
sion criteria.
Inclusion criteria:
• written in English
• human studies
• clinical trial or randomized controlled design or presenting
cross-sectional or prospective data.
Exclusion criteria:
• case studies, reviews, and meta-analyses
• animal studies.
Figure 1 shows the selection methodology and number of articles. A
total of 318 articles from PubMed, 274 articles from Web of Science,
33 articles from Cochrane, and 25 articles from LILACS were found.
Articles were screened with a review process according to:
• title and abstract
• full-text examination.
According to the selection criteria, eight studies with prospective de-
sign, two studies with retrospective design, and three studies with
follow-up were included in this review. Heterogeneity of study de-
signs and study characteristics does not allow to conduct any statis-
tical analyses.
CLINICAL AND RESEARCH CONSEQUENCES
Studies have revealed controversial results for the relationship be-
tween caeine intake and reproductive health. The present review
aimed to review studies evaluating outcomes, fertility, and live births.
According to the literature search, 13 studies were included in this
review. Table 2 shows the study results.
Six studies revealed negative eects of caeine intake on reproduc-
tive health, two of them reported positive eects, and ve studies
found no association. According to studies that were included in
this review, Wilcox et al., Jensen et al., Bolumar et al., Klono-Cohen
et al., Wesselink et al., and Gaskins et al. reported negative eects
of caeine, coee, or tea intake on reproductive health parameters
(2,4,8,21–23). Hatch et al. and Florack et al. reported a positive rela-
tionship (24,25). However, Hakim et al., Taylor et al., Chavarno et al.,
Curtis et al., and Caan et al. found no association (26–30).
First, studies that found a negative association of caeine determined
the FRs as an outcome. Wilcox et al. conducted the rst study that
reported a negative association between caeine and fecundability.
They found 50% lower FRs in the group who consumed high amounts
of caeine (21). Jensen et al. found that more than 700 mg/day caeine
Clin Exp Health Sci 2018; 8: 138-45 Macit et al. Fertility and Caeine Intake
139
Table 1. Amount of caeine in some foods and beverages.
Foods and beverages Caeine content (mg)
Filter coee (200 mL) 90
Espresso (60 mL) 80
Black tea (220 mL) 50
Green tea (220 mL) 24
Coke (335 mL) 40
Plain chocolate (50 g) 50
Milk chocolate (50 g) 10
Standard energy drink (250 mL) 80
United States Department of Agriculture, Agricultural Research Service, USDA
Food Composition Databases. Available from: https://ndb.nal.usda.gov/ndb/
search/list (5).
European Food Safety Authority. Available from: http://www.efsa.europa.eu/sites/
default/les/corporate_publications/les/efsaexplainscaeine150527.pdf (6).

intake is associated with reduced fecundability among non-smokers
(men, OR: 0.47, 95% CI: 0.26–0.82 and female, OR: 0.63, 95% CI: 0.25–
1.60) (2). They reported the eect of caeine with reduced clearance
during the luteal phase and accumulation in implantation. Among
smokers, fecundability was decreased when caeine intake was more
than 300 mg/day among non-smokers (OR: 0.74, 95% CI: 0.59–0.92)
(20). It was stated that smokers may consume more caeinated bev-
erages, and smoking also enhances the metabolism of caeine via the
induction of hepatic cytochrome P-450 enzymes and increases N-de-
methylation (27). Caeine is the rst-choice substrate for CYP1A2 and
is often used for phenotyping of human cytochrome P450 (31,32).
Smoking also increases the metabolism of xanthine oxidase activity
and caeine (4). Bolumar et al. also reported that a 501 mg/day caf-
feine intake is associated with subfecundity (OR: 1.03–2.04, 95% CI:
1.45). Contradictory to these results, the association was stronger in
smokers. They explained this dierence in previous studies that heavy
coee drinkers smoke more (4).
Gaskins et al. examined the Nurses’ Health Study II (1991–2009) co-
hort and reported the eects of caeine consumption (23). When
caeine intake was categorized, there was a positive linear trend
across categories of pre-pregnancy caeine intake and risk of sponta-
neous abortion such that women consuming >400 mg/day had 1.11
(95% CI: 0.98–1.25) times the risk of spontaneous abortion compared
Clin Exp Health Sci 2018; 8: 138-45Macit et al. Fertility and Caeine Intake
140
Figure 1. Selection methodologhy of articles

Clin Exp Health Sci 2018; 8: 138-45 Macit et al. Fertility and Caeine Intake
141
Table 2. Overview of studies.
Studies Year Sample Study design Method Country Outcome
Adjust-
ment Inclusion Exclusion Results
Hakim et
al. (26)
1998 124
females
(23–41
years)
Prospective
observational
Steroid hormones and human
chorionic gonadotropin assess-
ment (urine), caeine intake (food
frequency for the last 1 month),
caeine content for coee: 100
mg, tea: 40 mg, cola: 50 mg
Caeine intake classication:
0–25 mg, 26–100 mg, 101–300
mg,
≥301 mg
America Probability
of concep-
tion per 100
menstrual
cycles
Smoking,
alcohol, age,
intercourse
frequency
Women
with repro-
ductive
Using oral
contracep-
tive and
intrauterine
device
Caeine (mg/day) n
Birth/no. of menstru-
ation
0–25 30 39/196 (19.9)
26–100 32 26/184
(14.1)
101–300 53 28/258
(10.9)
≥300 9 6/40 (15.0)
Jensen
et al. (2)
1998 430
couples
(20–35
years)
Follow-up
(3 years)
Follow-up for 6 menstruation
cycles or until conception
Intercourse frequency, reproduc-
tive health, vaginal bleeding
Semen sample
Caeine intake: daily or weekly
Caeine content
1 cup of coee: 100 mg,
1 cup of tea: 50 mg, 1 cup of
chocolate beverage: 25 mg, 0.25 L
cola: 100 mg, 50 g chocolate bar:
12.5 mg
Caeine classication:
0–299 mg, 300–699 mg, >700 mg
Denmark Each cycle
(pregnant
or not
pregnant)
BMI and
alcohol
intake,
diseases of
the female
reproduc-
tive organs,
semen
quality, and
duration
of the
menstrual
cycle
Not having
a child
before, not
using birth
control
methods
Among non-smokers,
intake of more than 700
mg/day
Caeine was associated
with an FR of 0.63
(95% CI:
0.25–1.60) among
females and 0.47 (95%
CI: 0.26–0.82) males
Bolumar
et al. (4)
1997 3187
females
(25–44
years)
Retrospective Conception time, caeinated
beverage consumption
Caeine content:
Tea: 40 mg, cola: 50 mg,
coee: 130 mg for Denmark, 115
mg for South Europe, 115 mg for
Germany (according to coee
type, size of cup, and brewing
method)
Caeine classication:
0–100, 101–300, 301–
500, and ≥501 mg
Conception time: 0–3.4, 3.5–9.4,
9.5–15.4 and >15.5
Denmark,
Germany,
Italy,
Poland,
Spain
Conception
time
Age (20,
21–25,
26–30,
31 years),
smoking for
the last 12
months
≥501 mg caeine in-
take is associated with
subfecundity
(OR: 1.03–2.04,
95% CI: 1.45)
Curtis et
al. (29)
1997 2607
(planned
pregnan-
cies <44
years)
Retrospective
cohort
Daily coee, tea, and cola con-
sumption
Caeine content for coee: 100
mg, tea: 40 mg, cola: 50 mg
Canada ––Planned
pregnancies
Using oral
contracep-
tive, trying
to become
pregnant
more than 1
year
There was no relation-
ship between caeine
intake and fertility
(<100 mg and >100
mg). Coee intake in
women and tea intake
in men were associated
with FR (0.92, 95% CI:
0.84–1.00 and 0.85,
95% CI: 0.69–1.05,
respectively)
Caan
et al. (30)
1998 187
females
Follow-up Food frequency (last 1 month) America –Age, BMI,
frequency of
intercourse,
smoking,
and alcohol-
ic beverages
Women
planning for
pregnancy
There was no relation-
ship between caeine
intake and fertility.
However, an increase
in tea intake caused a
decreased in getting
pregnant (OR: 7.25,
95% CI: 3.06–17.17)
Klono-
Cohen et
al. (22)
2002 221
couples
(M =
22–55
years,
F = 26–49
years)
Prospective Daily coee (100 mg), tea (50 mg),
and cola (50 mg) consumption
Caeine intake: 0–2 mg, 2–50 mg,
50–200 mg, >200 mg
America Oocyte
retrieval,
fertilization,
multiple
pregnancies
abortus, live
birth
Smoking,
alcohol, age,
ethnicity,
number
of embryo
transfer,
education,
parity,
treatment
type
Couples
with in vitro
fertilization
or gamete
intrafallopi-
an transfer
therapy
There was no
association between
outcomes and caeine
intake during the study.
However, lifetime
caeine intake was a
risk factor (2–50 mg
and >50 mg) (OR:
3.1–3.9). In men, 100
mg increase in caeine
consumption increased
the risk for multiple
pregnancies

Clin Exp Health Sci 2018; 8: 138-45Macit et al. Fertility and Caeine Intake
142
Table 2. Overview of studies.
Studies Year Sample Study design Method Country Outcome
Adjust-
ment Inclusion Exclusion Results
Hatch
et al. (24)
2012 3628
(18–40
years)
Prospective
cohort
Caeine intake was assessed
at baseline and every 8 weeks
(coee, soda, tea, green tea)
Denmark Fecund-
ability
Age, BMI,
alcohol,
smoking,
relationship
frequency,
tea, coee
Women
with a
regular
relationship,
not using
oral con-
traception,
planning
pregnancy
(less than 12
months)
–Increase FR in women
who consumed
more than >300 mg
compared with <100
mg (FR = 1.04, 95% CI:
0.90–1.21). There was
an inverse association
with soda intake (0.89,
0.80–0.98; 0.85, 0.71–
1.02; 0.84, 0.57–1.25;
0.48 0.21–1.13)
Florack
et al. (25)
1994 259
females
(18–39
years)
Prospective
study
Smoking habits, alcohol
consumption, and caeine
intake (e.g., coee, tea, and cola
consumption) were evaluated
Holland Fecund-
ability
Non-medi-
cal hospital
workers
–Participants with a
moderate caeine
intake (400–700 mg/
day) showed a higher
fecundability than
those with a lower in-
take level (adjusted OR:
2.1, 95% CI: 1.2–3.7).
Heavy caeine intake
(>700 mg/day) among
partners was negatively
related to fecundability
when compared with
the lowest intake level
(adjusted OR: 0.6, 95%
CI: 0.3–0.97)
Wilcox et
al. (21)
1988 104
females
Follow-up Caeine intake:
coee: 100 mg, instant coee: 65
mg, tea: 50 mg, soft drinks: 40 mg
USA Fecund-
ability
Age, fre-
quency of
intercourse,
age at
menarche,
prenatal
exposure
to mother’s
smoking
Healthy
females
who were
planning
to become
pregnant
–Lower FR in the group
who consumed high
amounts of caeine
Gaskins
et al. (23)
2016 15,590
females
(20–44
years)
Prospective
cohort
Dietary intake: a 131-item Food
Frequency
Questionnaire
Caeinated coee: 137 mg
caeine/cup,
tea: 47 mg caeine/cup, caeinat-
ed sodas: 46 mg caeine/
bottle or can, and chocolate: 7 mg
caeine/serving
USA
(Nurses’
Health
Study II)
Sponta-
neous
abortion
Pre-preg-
nancy
caeine
intake
Female
nurses
–There is a positive
association between
caeine intake
and spontaneous
abortion that women
consuming >400 mg/
day had 1.11 (95% CI:
0.98–1.25) times the
risk compared with
women consuming
<50 mg/day (p<0.05)
Chavarro
et al. (28)
2009 18,555
females
(24–42
years)
Prospective,
cohort (Nurses’
Health Study
II), follow-up (8
years)
Food frequency (2 times),
ovulatory disorder, infertility
reported
America Fertility Age,
total energy
intake
Women
without
infertility
history
Women
with dia-
betes
438 ovulatory
disorder infertilities
were assessed after
follow-up. There was
no relationship with
caeine intake
Taylor et
al. (27)
2011 319
females
(20–41
years)
Prospective Daily caeine intake
1 cup of coee: 150 mg,
1 cup of tea: 55 mg,
1 cup of cola: 45 mg
Caeine classication:
<150 mg, 150–300 mg, >300 mg
America Fecund-
ability
Age, BMI,
intercourse
without,
planning
pregnancy,
alcohol,
smoking
Participants
with N-acet-
yltransferase
2 polymor-
phisms (161
slow, 158
fast acetyla-
tors)
Hormonal
contra-
ceptive,
intrauterine
device, in-
fertility (not
having a
conception
more than
1 year), hys-
terectomy,
polycystic
ovary, tube
ligation,
vasectomy
There was no relation-
ship between caeine
and FR

with women consuming <50 mg/day (p=0.05). Interestingly, when
beverages were evaluated separately, both caeinated and decaf-
feinated coee intakes had a positive association with spontaneous
abortion (p=0.01 and 0.04, respectively). These results need to be
taken into consideration, and further studies should be conducted
on non-caeinated beverages. The possible mechanism associated
with pre-pregnancy coee intake and risk of spontaneous abortion
was explained by the eects of coee on endogenous sex hormone
metabolism, pregnanediol-3-glucuronide levels, lower total and free
luteal plasma estradiol levels, and higher 2-catechol estrogen metab-
olites, 2-hydroxyestrone, and 2-hydroxyestradiol (23).
Klono-Cohen et al. stated that there is no association between caf-
feine and fertilization (22). However, lifetime caeine consumption
was a risk factor for no birth. The possible mechanisms were ex-
plained with the reduced levels of reproductive hormones such as
estradiol. In a recent study, Wesselink et al. found a negative associa-
tion between caeine and fecundability in males but not in females
(8). According to the results of their study, ≥300 mg/day caeine con-
sumption was associated with decreased fecundability among males
(M = 0.72, 95% CI: 0.54–0.96). It was emphasized that low caeine
intake of cohort may weaken the associations. Hatch et al. also re-
ported that there is a minor negative eect of caeine on reproduc-
tive systems for participants who consumed more than 300 mg/day
caeine (24). They claimed that this association may be stronger in
less fertile women.
Hakim et al. found no relationship with daily coee intake on births
(26). However, they found a decrease in the probability of concep-
tion that consumed alcohol and claimed that caeine may worsen
the eects of alcohol. Separate analyses were also conducted on
participants who did not consume alcohol or cigarette. It was stat-
ed that there is also a decrease, though not statistically signicant,
conception rate in women who consumed more than one cup of
coee (18.0%, adjusted OR: 0.56). Hakim et al. also reported that the
association may occur even in low intakes than previous studies sug-
gested for more than three cups of intakes (26). Similar to their study,
Curtis et al. found no association between caeine and fertility (29).
However, they reported that fecundability is decreased in females
who consumed coee and in males who consumed tea (0.92, 95%
CI: 0.84–1.00 and 0.85, 95% CI: 0.69–1.05, respectively). These results
that were explained with the possibility of bias by misclassication
of caeine exposure were consistent with the literature that found
reduced FRs.
Caan et al. also could not nd any statistically signicant decrease in
fertility in terms of caeine intake (30). Their study was conducted on
187 participants; it was a small sample size compared with the stud-
ies with large cohorts (4,27). The aim of their study was to prevent
bias in which retrospective studies might involve and assess odds ra-
tios with an 80% power. This power ratio may still be not enough to
detect the relationship.
Chavarro et al. conducted a study with a large cohort (Nurses’ Health
Study II), with 18,555 women with a long follow-up (8 years) (28).
After the follow-up period, 438 ovulatory disorder infertilities were
reported but no positive association between the intake of caeine,
coee, tea, or decaeinated coee and risk of ovulatory infertility.
They emphasized the lack of methodological design of retrospective
studies, which Leviton and Cowan discussed in detail in their study
(32). Taylor et al. (27) evaluated the eects of caeine with a similar
design but smaller sample size compared with Chavarro et al. (28).
Their study conducted on women who had N-acetyltransferase 2
(NAT2) polymorphisms also failed to nd an association; however,
the relationship was assessed regardless of NAT2 acetylation status.
In this review, caeine consumption was evaluated in terms of
pre-pregnancy. In pregnancy, caeine intake should also be consid-
ered. Buck Louis et al. reported that more than two daily caeinated
drinks are signicantly associated with pregnancy loss (preconcep-
tion [aHR 1/4 1.74, 1.07–2.81], early pregnancy [aHR 1/4 3.05, 1.75–
5.34], and periconception [aHR 1/4 2.58, 1.56–4.27]) (33). Their study
provides a dierent perspective on the ow of the present review
and supports the idea to decrease caeine consumption after preg-
nancy especially in the rst trimester in which Gaskins et al. reported
higher rates of spontaneous abortion (23).
When we evaluate the studies on caeine in terms of consumption
amounts (mg), the negative eect of caeine on reproductive health
ranges between 300 and 700 mg/day. However, taking into consid-
eration coee consumption, this amount decreases to 100 mg/day.
Even if 200 mg/day caeine intake is determined as a maximum in-
take for pregnant women, the eect of coee at 100 mg/day intake
supports the idea to decrease the consumption as much as possible.
CONCLUSION
There are several studies about caeine consumption and repro-
ductive health. However, dierent designs make it more dicult to
Clin Exp Health Sci 2018; 8: 138-45 Macit et al. Fertility and Caeine Intake
143
Table 2. Overview of studies.
Studies Year Sample Study design Method Country Outcome
Adjust-
ment Inclusion Exclusion Results
Wes-
selink et
al. (8)
2016 2135
females
(21–45
years)
Prospective
cohort
Daily consumption of beverages
(coee: 135 mg, decaeinated
coee: 5.6 mg, black tea: 20 mg,
green tea: 20 mg, white tea: 15
mg, soda: 23–69 mg, energy
drink: 48–280 mg)
America/
Canada
Fecund-
ability
Age, eth-
nicity, BMI,
smoking,
alcohol,
relationship
frequency,
stress, sleep,
working
time,
methods
to increase
pregnancy
probability
21–45 years,
not using
contra-
ception,
not having
fertility
treatment
Women
with
irregular
menstrual
cycle
There was no asso-
ciation for women;
however, an increase
in caeine intake was
related with a decrease
in FR (FR ≥300 vs. <100
mg/day = 0.72, 95% CI:
0.54–0.96)
BMI, body mass index.

compare results. Some of the studies focus on caeine consumption,
whereas some of them focus only on coee consumption owing
to its high caeine content. Focusing on coee intake alone would
probably result in underestimations of total caeine intake. Accord-
ing to dierent countries, caeine intake might dier, and chocolate,
black tea, or green tea may become an important source of caeine.
Additionally, coee consumption is evaluated as “one cup of coee”
or “one serving”. Nevertheless, type of coee beans, brand, roasting
degree (soft, medium, and dark roasted), infusion time, and cup size
aect coee content. These covariates should be considered in study
designs. In addition, retrospective studies tend to show more rela-
tionship between caeine intake and fertility which may be a result
of asseseing caeine intake with retrospective questionnaire. After
analyzing the study designs, it becomes dicult to give a clear rec-
ommendation, but if these study results are considered, it may be
advisable for couples who are planning to conceive to decrease caf-
feine intake as much as possible, especially from coee. There are
also other caeine sources, but coee is the main source of caeine
in the diet. It may also be recommended to consume other sources of
healthy beverages and foods if there is a need. Further studies with a
detailed design and accurate measurement of caeine intake should
be conducted to clarify the eects of caeine including decaeinat-
ed beverages.
Limitations
The selected studies dier in quality of information, study design,
and categorization of caeine exposure. These study limitations af-
fect the present study and make it dicult to present an extensive
recommendation. Nevertheless, these limitations reveal the need for
an accurate assessment of caeine intake. Individual assessment of
dietary intake may be useful instead of standard questionnaires.
Peer-review: Externally peer-reviewed.
Author contributions: Concept – M.S.M, Y.A.; Design - M.S.M, Y.A.; Supervi-
sion - Y.A.; Resource M.S.M.; Materials - M.S.M.; Data Collection and/or Process-
ing - M.S.M.; Analysis and/or Interpretation - M.S.M.; Literature Search - M.S.M.;
Writing - M.S.M., Y.A.; Critical Reviews - M.S.M., Y.A.
Conict of Interest: The authors have no conict of interest to declare.
Financial Disclosure: The authors declared that this study has received no
nancial support.
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