Milk and dairy consumption and incidence of cardiovascular diseases
and all-cause mortality: dose-response meta-analysis of prospective
Sabita S Soedamah-Muthu, Eric L Ding, Wael K Al-Delaimy, Frank B Hu, Marielle F Engberink, Walter C Willett, and
Johanna M Geleijnse
Background: The consumption of dairy products may influence the
risk of cardiovascular disease (CVD) and total mortality, but con-
flicting findings have been reported.
Objective: The objective was to examine the associations of milk,
total dairy products, and high- and low-fat dairy intakes with the
risk of CVD [including coronary heart disease (CHD) and stroke]
and total mortality.
Design: PubMed, EMBASE, and SCOPUS were searched for ar-
ticles published up to February 2010. Of .5000 titles evaluated, 17
met the inclusion criteria, all of which were original prospective
cohort studies. Random-effects meta-analyses were performed with
summarized dose-response data. Milk as the main dairy product was
pooled in these analyses.
Results: In 17 prospective studies, there were 2283 CVD, 4391
CHD, 15,554 stroke, and 23,949 mortality cases. A modest inverse
association was found between milk intake and risk of overall CVD
[4 studies; relative risk (RR): 0.94 per 200 mL/d; 95% CI: 0.89,
0.99]. Milk intake was not associated with risk of CHD (6 studies;
RR: 1.00; 95% CI: 0.96, 1.04), stroke (6 studies; RR: 0.87; 95% CI:
0.72, 1.05), or total mortality (8 studies; RR per 200 mL/d: 0.99;
95% CI: 0.95, 1.03). Limited studies of the association of total dairy
products and of total high-fat and total low-fat dairy products (per
200 g/d) with CHD showed no significant associations.
Conclusion: This dose-response meta-analysis of prospective stud-
ies indicates that milk intake is not associated with total mortality
but may be inversely associated with overall CVD risk; however,
these findings are based on limited numbers.
Am J Clin Nutr
Cardiovascular disease(CVD) isthemain causeof deathin the
Western world,claiming 17million livesperyear (1). The burden
from coronary heart disease (CHD) as its main component is
projected to rise from ’47 million disability-adjusted life-years
in 1990 (DALY = healthy years of life lost) to 82 million DALYs
in 2020 (1). It has been postulated that the consumption of dairy
products influences the risk of CVD (including CHD and stroke)
or all-cause mortality, but findings from epidemiologic studies
have been conflicting. Several prospective cohort studies have
suggested inverse associations of milk in particular with stroke
(2–5), but also with CHD (3) and all-cause mortality (6).
Whereas other cohort studies reported that milk was positively
associated with CHD (7) or stroke (8). Many studies also re-
ported no significant association between milk and CHD (9–13),
stroke (14, 15), or all-cause mortality (16–19). Total dairy intake
was rarely reported (compared with milk) and yielded conflict-
ing evidence, with no relation to CHD (20, 21). Meanwhile,
high-fat dairy product consumption has been shown to be pos-
itively related to CHD (22, 23), whereas low-fat dairy product
consumption has been shown to be inversely associated with
CHD (22) or stroke (15).
The mechanisms by which dairy products can exert certain
effects on CVD are diverse, with divergent mechanisms sug-
gesting both positive and negative influences. Dairy products are
rich in minerals (calcium, potassium, and magnesium), protein
(casein and whey), and vitamins (riboflavin and vitamin B-12)
that can exert beneficial effects on CVD. On the other hand,
saturated fat in dairy products can adversely influence CHD,
although the effect of saturated fat on CHD risk depends on the
source of calories (unsaturated fatty acids or carbohydrates) by
which it is substituted to maintain energy balance (24). There is
some suggestion that low-fat dairy products may beneficially
influence blood pressure (25, 26). Studies have shown that the
Dietary Approaches to Stop Hypertension (DASH) dietary
pattern—which is high in fruit, vegetables, nuts, fish, and low-fat
dairy products—lowers blood pressure effectively, which may in
part be attributed to its relatively high content of low-fat dairy
products (27). Whether these effects on blood pressure can be
specifically addressed by low-fat dairy products is not clear from
1From the Division of Human Nutrition, Wageningen University,
Wageningen, Netherlands (SSS-M, MFE, and JMG); the Department of
Nutrition and Epidemiology, Harvard School of Public Health, Boston,
MA (ELD, FBH, and WCW); the Channing Laboratory, Department of
Medicine, Brigham and Women’s Hospital and Harvard Medical School,
Boston, MA (ELD, FBH, and WCW); and the Department of Family and
Preventive Medicine, University of California, San Diego, San Diego, CA
2Supported by an unrestricted grant from the Dutch Dairy Association (to
SSS-M and JMG).
3Address correspondence and requests for reprints to SS Soedamah-Muthu,
Division of Human Nutrition, Wageningen University, PO Box 8129, 6700 EV
Wageningen, Netherlands. E-mail: firstname.lastname@example.org.
Received May 25, 2010. Accepted for publication September 30, 2010.
First published online November 10, 2010; doi: 10.3945/ajcn.2010.29866.
Am J Clin Nutr 2011;93:158–71. Printed in USA. ? 2011 American Society for Nutrition
at WAGENINGEN UNIV AND RESEARCH CENTRE on October 18, 2011
Supplemental Material can be found at:
DASH, but European guidelines on CVD prevention do rec-
ommend the DASH diet with low-fat dairy products, albeit such
a recommendation is not yet fully evidence-based (28). Two
meta-analyses (29, 30) and 2 narrativereviews (31, 32) combined
with individual studies produced conflicting conclusions. Com-
bining evidence from different study designs (ecologic, case-
control, and prospective) and different study populations (age,
sex, country, and various mean milk intakes) may explain the
conflicting results. Pooling different exposures (calcium and
milk) and the use of inappropriate statistical methods could also
lead to conflicting conclusions.
Therefore, we conducted a new systematic evaluation of the
association between intakes of milk, total dairy products, total
high-fat dairy products, and total low-fat dairy products with risk
of total CVD, CHD, stroke, and all-cause mortality via a dose-
response meta-analysis of prospective cohort studies in healthy
adult men and women.
SUBJECTS AND METHODS
Study selection for the meta-analysis
A systematic literature review was conducted by using the data-
bases PubMed (http://www.ncbi.nlm.nih.gov/pubmed), EMBASE
(http://www.embase.com), and SCOPUS (http://www.scopus.com)
from 10 February 2009 until 1 June 2009, based on the query
syntax shown in supplemental Table 1 (see “Supplemental data”
in the online issue ). An updated secondary search was con-
ducted until 22 February 2010. First, titles of the articles were
screened, on basis of which we excluded animal studies, chil-
dren aged ,18 y, and diseased populations (including diabetes
and CVD). Second, abstracts of the articles were screened for the
following inclusion criteria: prospective cohort studies, original
articles, general population, dairy products as main exposure, and
fatal or nonfatal CVD (CHD and stroke) or mortality outcomes.
For articles that met the inclusion criteria, the full text was re-
trieved. An additional hand search for relevant articles was per-
formed by using bibliographies of scientific articles (eg, review
Dairy intake data as well as relative risks (RRs) for CVD,
CHD, stroke, and all-cause mortality (with 95% CIs) were
extracted from the selected articles. If insufficient data were
reported in the article (eg, absence of RRs, CIs, dairy intakes, or
number of cases), additional information was requested from the
authors (7, 14, 20–22). All data were extracted into a predefined
spreadsheet and checked several times. The selection and data
extraction process was executed by 2 independent reviewers
(SSS-M and JMG). If multiple articles were on the same study
sample with the same exposure and outcome [Caerphilly cohort
study (4, 10), Iowa Women’s Health study (9, 23)], only the
publication with the largest number of outcome cases was
retained. In one study population (Oxford Vegetarian Study) (7,
11), because different outcomes were reported in different arti-
cles, both articles on the same study population were included.
nonfatal CHD and stroke), CHD (fatal and nonfatal), stroke (fatal
and nonfatal), and all-cause mortality, defined as such in the
underlying studies. CVD was defined as CHD or stroke [WHO
International Classification of Diseases (ICD)-10 I60-69; http://
www.who.int/classifications/icd/en] and other CVD, including
cardiac arrest (I46), heart failure (I50), and sudden death (R96).
CHD was defined as acute myocardial infarction, angina pec-
toris, and other ischemic heart disease (as in ICD-10 I20-I25).
Dairy intakes were converted from servings or other units into
g/d by using standard conversions from the Food Standards
Agency (pint = 585 g; milk, 1 glass = 200 mL; and total dairy =
200 g) (33, 34). Assumptions were made to convert all dairy
exposure data into g/d or for milk into mL/d. For this 1 serving,
dairy products or milk were estimated to be on average 200 g or
200 mL, respectively.
We examined the association between milk consumption and
CVD, CHD, stroke, and all-cause mortality. Because there were
insufficient numbers of studies for dairy products and outcomes
other than CHD, we analyzed total dairy, total low-fat dairy, and
total high-fat dairy products only for CHD risk. There were
insufficient numbers of studies (?2) including certain exposures,
such as cheese, yogurt, and high-fat or low-fat milk; therefore,
these analyses could not be pursued.
Only studies with similar exposures and outcomes were pooled
We used STATAversion 11.0 (StataCorp, College Station, TX)
for meta-analysis using the METAN command, whereas dose-
response meta-analyses were conducted by using the GLST
command with the generalized least-squares method for trend
estimation of summarized dose-response data, based on the
Greenland and Longnecker method (35). All statistical tests
were 2-sided with a = 0.05. Restricted cubic splines were used to
assess for potential curvilinear relations.
Between-study heterogeneity was assessed via the I2statistic
(36), which expresses the percentage of variation attributable to
between-study heterogeneity. Random-effects pooling were con-
ducted by using DerSimonian and Laird random-effects models
(37). Forest plots were made for the relation between milk or
dairy and CVD, CHD, stroke, and all-cause mortality. From each
publication, we used the results from the main multivariable
model that included most confounders. Subgroup analyses were
performed by sex, age (young compared with old), continent, and
degree of adjustment for confounding, providing sufficient num-
bers of studies. For year of publication and BMI, variation was
insufficient across studies to conduct subgroup analyses. To assess
whether studies of lesser quality could have influenced the results,
meta-analyses were split by categorizing studies by whether or
not they adjusted for the most essential confounders (age, sex,
BMI, smoking, and total energy intake). Most of the associations
were not adjusted for physical activity or other aspects of diet,
including intakes of fruit and vegetables and specific fatty acids;
therefore, these could not be included.
To explore heterogeneity with a statistical test, further meta-
regression analyses were performed to relate the size of effect to
one or morecharacteristics(age, sex, and confounderadjustments)
of the studies involved. In addition, interaction terms were added,
mortality, which included most studies (n = 8), we used a funnel
plot to assess the presence of publication bias. In addition, we
DAIRY AND CVD META-ANALYSIS
at WAGENINGEN UNIV AND RESEARCH CENTRE on October 18, 2011
lung, stomach, and breast. Higher consumption of milk and dairy
55). On the contrary, there was also suggestive evidence of an
inverse association between milk intake and colon cancer (56)
and possibly bladder cancer. For other health outcomes such as
Parkinson disease, dairy products may increase its risk (57).
Furthermore, the risk of hip or bone fractures does not seem to be
associated with higher consumption of dairy products (58, 59). In
summary, evidence from the literature on other health outcomes
does not really support strong recommendations of increasing
intakes of milk and dairy products.
Overall, this study showed no association between milk and
total mortality, but modest inverse associations with CVD. Milk
and dairy products cannot be recommended to benefit CVD
health outcomes on the basis of this dose-response meta-analysis.
Intake of milk and dairy products does not seem to be harmful,
but whether the association is truly inverse cannot be firmly
concluded. Further studies arewarranted to investigate the relation
between consumption of dairy products and risk of CVD and to
investigate different dairy components separately with sufficient
follow-up to assess multiple health outcomes.
We thank all of the authors who contributed data to this meta-analysis: D
Feskanich (Nurses’ Health Study, stroke outcomes), M Thorogood (Oxford
Vegetarian Study, United Kingdom, CHD/mortality), and D Panagiotakos
(ATTICA Study). We thank DL Bouchaut (University of Wageningen, Nether-
lands) for her help on all of the figures in this manuscript, and RJ Harris (Uni-
versity of Bristol, United Kingdom) for his help with the STATA programming
of the dose-response meta-analyses.
The authors’ responsibilities were as follows—SSS-M: statistical design,
analysis of the data, and writing of the manuscript; ELD: statistical design,
reviewof the data analysis,and writing ofthe manuscript; WKA-D, FBH, and
WCW: contribution of data, interpretation of data, and writing of the manu-
script;MFE: writingof the manuscript; andJMG:principalinvestigatorofthe
meta-analysis dairy projects, funding, and writing of manuscript. All authors
directly participated in the planning, execution, or analysis of the study and
reviewed the manuscript. SSS-M and JMG obtained an unrestricted grant
from the Dutch Dairy Association to carry out this study. None of the other
authors had a conflict of interest. The sponsors were not involved in the con-
duct and writing of the manuscript.
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