Background:An elevated plasma homocysteine concentration is
a putative risk factor for cardiovascular disease. Observational
studies have reported an association between coffee consump-
tion and plasma homocysteine concentrations.
Objective: We studied the effect of coffee consumption on
plasma homocysteine in a crossover trial. We used unfiltered cof-
fee so as to include the possible effects of coffee diterpenes,
which are removed by filtering.
Design: Sixty-four healthy volunteers (31 men and 33 women)
with a mean (±SD) age of 43 ± 11 y were randomly assigned to
2 groups. One group (n = 30) drank 1 L unfiltered cafetière
(French press) coffee daily for 2 wk. Such coffee is rich in the
cholesterol-raising diterpenes kahweol and cafestol. The other
group (n = 34) received water, milk, broth, tea, and chocolate
drinks instead of coffee. After a washout period of 8 wk, both
groups received the alternate intervention for another 2 wk.
Results: Consumption of 1 L unfiltered coffee/d for 2 wk signi-
ficantly raised fasting plasma homocysteine concentrations by
10%, from 12.8 to 14.0 ?mol/L.
Conclusions: Unfiltered coffee increases plasma homocysteine
concentrations in volunteers with normal initial concentrations. It is
unclear whether the effect is caused by the cholesterol-raising diter-
penes present exclusively in unfiltered coffee or by factors that are
also present in filtered coffee.
Am J Clin Nutr 2000;71:480–4.
kahweol, cafestol, cardiovascular disease risk, humans, Netherlands
Unfiltered coffee, homocysteine, diet, diterpenes,
An elevated plasma homocysteine concentration is a putative risk
factor for coronary, cerebral, and peripheral vascular disease (1, 2).
Boushey et al (3) reported in a meta-analysis of homocysteine and car-
diovascular disease that 10% of all coronary artery disease events may
be explained by an elevated concentration of total plasma homocys-
teine. An elevated plasma homocysteine concentration can be caused
by genetic defects—eg, a mutation in the methylenetetrahydrofolate
reductase enzyme or heterozygosity for the cystathionine ?-synthase
deficiency—and by nongenetic factors. Examples of nongenetic fac-
tors are deficiencies in vitamin B-12, folate, and vitamin B-6 (4).
Other dietary factors might also affect plasma homocysteine. A
positive correlation between the plasma homocysteine concentra-
tion and coffee consumption was reported in 2 other studies (5, 6).
In Norway, 5916 healthy men and 6349 women aged 40–42 y were
studied. Average plasma homocysteine was 9.1 ?mol/L in coffee
abstainers and 11.2 ?mol/L in heavy coffee consumers, ie, those
who drank >8 cups coffee/d (5). Filtered coffee was purportedly
consumed by 96.4% of the subjects. No association was observed
between decaffeinated coffee consumption and plasma homocys-
teine. This suggests that the effect on homocysteine is due to caf-
feinated coffee. In the United States, an older population of 151
women and 109 men (median age: 64 y) was investigated. The
average plasma homocysteine concentration was 9.8 ?mol/L in
coffee abstainers and 11.1 ?mol/L in a population drinking an
average of 4 cups coffee/d (6). No detailed information on the type
of coffee brew was reported in this study.
However, an association between coffee consumption and plasma
homocysteine could not be confirmed in participants of the Athero-
sclerosis Risk in Communities Study in the United States (7). In this
study, there was also no detailed information on the type of coffee
brew reported. The inconsistencies between these observational stud-
ies suggest that not all types of coffee brew have the same effect on
plasma homocysteine concentrations or that the effect is spurious.
We therefore studied the effect of coffee on total plasma homocys-
teine in healthy volunteers in a placebo-controlled crossover trial.
This study was part of a study in which we investigated the influence
of coffee on biomarkers for colonic cancer. We used unfiltered cof-
Am J Clin Nutr 2000;71:480–4. Printed in USA. © 2000 American Society for Clinical Nutrition
Unfiltered coffee increases plasma homocysteine concentrations in
healthy volunteers: a randomized trial1–3
Marina J Grubben, Godfried H Boers, Henk J Blom, Roelinka Broekhuizen, Romy de Jong, Leonie van Rijt, Eke de Ruijter,
Dorien W Swinkels, Fokko M Nagengast, and Martijn B Katan
1From the Departments of Gastroenterology and Hepatology, Internal
Medicine, Pediatrics, and Clinical Chemistry, University Hospital Nijmegen,
Netherlands, and the Department of Human Nutrition and Epidemiology,
Agricultural University Wageningen, Netherlands.
2Supported by grants from the Netherlands Digestive Diseases Foundation
(95-55) and the Netherlands Foundation for Nutrition and Health Research.
HJ Blom is an Established Investigator of the Netherlands Heart Foundation
3Address reprint requests to MJ Grubben, Department of Gastroenterol-
ogy and Hepatology, University Hospital Nijmegen, PO Box 9101, 6500 HB
Nijmegen, Netherlands. E-mail: M.Grubben@gastro.azn.nl.
Received May 24, 1999.
Accepted for publication September 9, 1999.
See corresponding editorial on page 403.
by guest on January 19, 2016