Systematic Review of the Association between Dairy Product Consumption and Risk of Cardiovascular-Related Clinical Outcomes

Abstract

The objective of this systematic review was to determine if dairy product consumption is detrimental, neutral, or beneficial to cardiovascular health and if the recommendation to consume reduced-fat as opposed to regular-fat dairy is evidence-based. A systematic review of metaanalyses of prospective population studies associating dairy consumption with cardiovascular disease (CVD), coronary artery disease (CAD), stroke, hypertension, metabolic syndrome (MetS), and type 2 diabetes (T2D) was conducted on the basis of the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. Quality of evidence was rated by using the Grading of Recommendations Assessment, Development, and Evaluation scale. High-quality evidence supports favorable associations between total dairy intake and hypertension risk and between low-fat dairy and yogurt intake and the risk of T2D. Moderate-quality evidence suggests favorable associations between intakes of total dairy, low-fat dairy, cheese, and fermented dairy and the risk of stroke; intakes of low-fat dairy and milk and the risk of hypertension; total dairy and milk consumption and the risk of MetS; and total dairy and cheese and the risk of T2D. High- to moderate-quality evidence supports neutral associations between the consumption of total dairy, cheese, and yogurt and CVD risk; the consumption of any form of dairy, except for fermented, and CAD risk; the consumption of regular- and high-fat dairy, milk, and yogurt and stroke risk; the consumption of regular- and high-fat dairy, cheese, yogurt, and fermented dairy and hypertension risk; and the consumption of regular- and high-fat dairy, milk, and fermented dairy and T2D risk. Data from this systematic review indicate that the consumption of various forms of dairy products shows either favorable or neutral associations with cardiovascular-related clinical outcomes. The review also emphasizes that further research is urgently needed to compare the impact of low-fat with regular- and high-fat dairy on cardiovascular-related clinical outcomes in light of current recommendations to consume low-fat dairy.

Full text

REVIEW
Systematic Review of the Association between
Dairy Product Consumption and Risk of
Cardiovascular-Related Clinical Outcomes
1–3
Jean-Philippe Drouin-Chartier,
4
Didier Brassard,
4
Maude Tessier-Grenier,
4
JulieAnneCôté,
5
Marie-Ève Labonté,
6
Sophie Desroches,
4
Patrick Couture,
4,7
and Benoît Lamarche
4
*
4
Institute of Nutrition and Functional Foods, Laval University, Quebec City, Quebec, Canada;
5
Institut Universitaire de Cardiologie et de
Pneumologie de Québec, Quebec City, Quebec, Canada;
6
Department of Nutritional Science, Faculty of Medicine, University of Toronto, Toronto,
Ontario, Canada; and
7
CHU de Québec-Université Laval, Quebec City, Quebec, Canada
ABSTRACT
The objective of this systematic review was to determine if dairy product consumption is detrimental, neutral, or beneficial to cardiovascular
health and if the recommendation to consume reduced-fat as opposed to regular-fat dairy is evidence-based. A systematic review of meta-
analyses of prospective population studies associating dairy consumption with cardiovascular disease (CVD), coronary artery disease (CAD),
stroke, hypertension, metabolic syndrome (MetS), and type 2 diabetes (T2D) was conducted on the basis of the PRISMA (Preferred Reporting
Items for Systematic Reviews and Meta-Analyses) statement. Quality of evidence was rated by using the Grading of Recommendations
Assessment, Development, and Evaluation scale. High-quality evidence supports favorable associations between total dairy intake and
hypertension risk and between low-fat dairy and yogurt intake and the risk of T2D. Moderate-quality evidence suggests favorable associations
between intakes of total dairy, low-fat dairy, cheese, and fermented dairy and the risk of stroke; intakes of low-fat dairy and milk and the risk of
hypertension; total dairy and milk consumption and the risk of MetS; and total dairy and cheese and the risk of T2D. High- to moderate-quality
evidence supports neutral associations between the consumption of total dairy, cheese, and yogurt and CVD risk; the consumption of any
form of dairy, except for fermented, and CAD risk; the consumption of regular- and high-fat dairy, milk, and yogurt and stroke risk; the
consumption of regular- and high-fat dairy, cheese, yogurt, and fermented dairy and hypertension risk; and the consumption of regular- and
high-fat dairy, milk, and fermented dairy and T2D risk. Data from this systematic review indicate that the consumption of various forms of dairy
products shows either favorable or neutral associations with cardiovascular-related clinical outcomes. The review also emphasizes that
further research is urgently needed to compare the impact of low-fat with regular- and high-fat dairy on cardiovascular-related clinical outcomes
in light of current recommendations to consume low-fat dairy. Adv Nutr 2016;7:1026–40.
Keywords: dairy, milk, cheese, yogurt, cardiovascular disease, coronary artery disease, stroke, hypertension, metabolic syndrome, type 2 diabetes
Introduction
The consumption of dairy, particularly low-fat dairy, is ad-
vocated in most dietary guidelines around the world. The
main argument supporting the recommendation to consume
low-fat dairy is that high plasma LDL-cholesterol concentra-
tions are a key risk factor for coronary artery disease (CAD)
8
and that regular- and high-fat dairy foods are a major source
2
Author disclosures: D Brassard, M Tessier-Grenier, JA Co
ˆte
´, and M-E
`Labonte
´, no conflicts of
interest. B Lamarche is Chair of Nutrition at Laval University. This Chair is supported by
unrestricted endowments from the Royal Bank of Canada, Pfizer, and Provigo/Loblaws. He
has received funding in the last 5 y for his research from the Canadian Institutes of
Health Research (CIHR), Natural Sciences and Engineering Research Council of Canada,
Agriculture and Agrifood Canada, the Canola Council of Canada, Dairy Farmers of Canada
(DFC), the Dairy Research Institute (DRI), Atrium Innovations, the Danone Institute, and Merck
Frosst. He has received speaker honoraria over the last 5 y from DFC and the DRI. He is Chair
of the Expert Scientific Advisory Panel of DFC and of the ad hoc committee on saturated fat of
the Heart and Stroke Foundation of Canada. P Couture has received funding in the last 5 y from
the CIHR, Agriculture and Agrifood Canada, DFC, DRI, Merck Frosst, and Kaneka Corporation.
S Desroches has received funding in the last 5 y from the CIHR and the Danone Institute.
J-P Drouin-Chartier has received speaker honoraria over the last year from DFC.
1
J-PD-C is a recipient of doctoral scholarships from the Canadian Institute of Health
Research and the Fonds de Recherche du Que
´bec – Sante
´. JAC is a recipient of the
Alexander-Graham-Bell doctoral scholarship from the Natural Sciences and Engineering
Research Council of Canada. M-EL is a recipient of a Canadian Institutes of Health
Research Fellowship (MFE-140953). This review was supported in part by an unrestricted
grant from the Dairy Research Consortium (Dairy Farmers of Canada, Centre National
Interprofessionnel de l’E
´conomie Laitie
`re, the Dairy Research Institute, Dairy Australia
Ltd., the Dutch Dairy Association (NZO), the Danish Dairy Research Foundation, as well as
by the Chair of Nutrition at Laval University. This is a free access article, distributed under
terms (http://www.nutrition.org/publications/guidelines-and-policies/license/) that
permit unrestricted noncommercial use, distribution, and reproduction in any medium,
provided the original work is properly cited.
1026 ã2016 American Society for Nutrition. Adv Nutr 2016;7:1026–40; doi:10.3945/an.115.011403.
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of cholesterol-increasing SFAs (1, 2). Although there is little
doubt about the LDL cholesterol–increasing effects of SFAs
per se, the extent to which the consumption of different
forms of dairy products, including regular- and low-fat
dairy, influences the risk of cardiovascular-related clinical
outcomes has not yet been comprehensively examined, to
our knowledge.
In an attempt to shed light on this complex issue, we have
undertaken a systematic review to answer the following 2
key questions: 1) is dairy consumption detrimentally, neu-
trally, or beneficially associated with cardiovascular-related
clinical outcomes, and 2) is the recommendation to consume
low-fat, as opposed to regular- or high-fat dairy, evidence-
based? This review focuses primarily on existing meta-analyses
of prospective epidemiologic studies of dairy intake and
cardiovascular-related clinical outcomes, that is, cardiovascular
disease (CVD), coronary artery disease (CAD), stroke, hyper-
tension, metabolic syndrome (MetS), and type 2 diabetes
(T2D). Prospective epidemiologic studies of dairy intake
and clinical outcomes of interest that were not included in
published meta-analyses were also further reviewed. The as-
sociation between dairy consumption and cardiovascular-
related outcomes was ascertained while considering total and
individual dairy (milk, yogurt, cheese), irrespective of fat con-
tent; regular- or high-fat and low-fat dairy as per the defini-
tion by investigators in the various studies; and finally,
fermented dairy when possible. Butter is generally not considered
part of the dairy food category in most dietary guidelines and
thus was not included in this analysis. We believe that this ex-
tensive review encompasses all available epidemiologic evidence
relating dairy product consumption to cardiovascular-related
health outcomes. No a priori hypothesis was established.
Methods
Full details of the methods used are presented in the Supplemental Methods.
Briefly, this systematic review was conducted according to the PRISMA (Pre-
ferred Reporting Items for Systematic Review and Meta-Analysis) statement
(Supplemental Table 1) (3). We first screened PubMedand Embase databases
to identify meta-analyses of prospective cohort studies on the association
between dairy product consumption (any form) and cardiovascular-related
clinical outcomes (e.g., CVD, CAD, stroke, hypertension, MetS, and T2D).
Meta-analyses of data from cross-sectional or case-control studies were not
included. Individual prospective cohort studies that had not been included
in the retrieved meta-analyses were also identified and reviewed. Two au-
thors independently undertook the literature search in May 2015 with the
use of keywords provided in Supplemental Table 2. The search was re-
peated in November 2015 before the original submission of the article
and updated in March 2016 during the revision process.
The quality of each meta-analysis was evaluated and scored by 2 authors
(J-PD-C and BL) independently by using the Meta-analysis Of Observa-
tional Studies in Epidemiology (MOOSE) checklist (4), as detailed in the
Supplemental Methods. The interrater reliability in the quality scoring
was good (r= 0.79). Disagreement between raters (scores differing by >15%)
was resolved by discussion. Meta-analyses with scores >80% were considered
to be of good quality. Studies with scoresbetween >60% and #80% were con-
sidered to be of moderate quality. Finally, studies with scores #60% were con-
sidered to be of poor quality. The complete list of meta-analyses included
in this systematic review and their quality rating is presented in Table 1.
The flow of retrieved meta-analyses and prospective cohort studies during
the literature search is shown in Supplemental Tables 3 and 4.
The quality of evidence relating dairy intake to cardiovascular-related
clinical outcomes was assessed through consensus from 2 authors (J-PD-C
and BL) by using an adaptation of the Grading of Recommendations Assess-
ment, Development, and Evaluation (GRADE) scale (26), as detailed in
Supplemental Table 5. According to the GRADE scale (27, 28), high-quality
evidence defines a situation in which “we are very confident that the true ef-
fect lies close to that of the estimate of the effect.”Moderate-quality evidence
indicates that “we are moderately confident in the effect estimate. The true
effect is likely to be close to the estimate of the effect, but there is a possibility
that it is substantially different.”Low-quality evidence indicates that “our
confidence in the effect estimate is limited. The true effect may be substan-
tially different from the estimate of the effect.”Very low-quality evidence in-
dicates that “we have very little confidence in the effect estimate. The true
effect is likely to be substantially different from the estimate of the effect.”
Information pertaining specifically to associations supported by low- or
very low-quality evidence has been included in the Supplemental Information
in order to shorten the review. Setting this information as online supporting
material should not be seen as a biased way to present the evidence, and we
emphasize in each section of this review the importance of conducting
more research in instances in which we are lacking high-quality evidence.
Dairy and Cardiovascular-Related Clinical
Outcomes
CVD
Total dairy and CVD. In 2013, O’Sullivan et al. (15) eval-
uated the association between total dairy intake and CVD
mortality (Supplemental Table 6). Total dairy intake showed
no association with CVD mortality rates (RR: 0.87; 95% CI:
0.62, 1.20). The authors reported no evidence of heterogene-
ity between studies and no publication bias. In their 2015
meta-analysis, Qin et al. (19) reported an inverse association
between total dairy consumption and the risk of nonfatal
CVD (RR: 0.88; 95% CI: 0.81, 0.96). There was no evidence
of significant heterogeneity between studies or publication
bias. Finally, Alexander et al. (24) recently reported no asso-
ciation between total dairy intake and CVD (RR: 0.85; 95%
CI: 0.75, 1.04), with significant heterogeneity between studies
but no publication bias. Two (15, 19) of the 3 meta-analyses
were based on different pools of cohort studies with only
1 study in common. Associations differed slightly according
to whether CVD mortality (15) or CVD incidence (19, 24)
was considered. The search retrieved 1 additional cohort
study (29) that had not been included in these meta-analyses
and that reported no significant association between total
dairy intake and risk of fatal CVD (Supplemental Table 7).
In summary, risk estimates based on 3 meta-analyses pre-
dicted either a favorable or neutral association between total
dairy consumption and CVD risk. Thus, there is moderate-
quality evidence that total dairy consumption is neutral in
terms of CVD risk (Table 2).
Dairy fat and risk of CVD. The quality of evidence relating
dairy fat intake to CVD risk is judged to be very low (Tab le 2 ),
when considering the lack of meta-analyses and the limited
3
Supplemental Methods, Supplemental Tables 1–15, and Supplemental Information are
available from the “Online Supporting Material” link in the online posting of the ar ticle and
from the same link in the online table of contents at http://advances.nutrition.org.
*To whom correspondence should be addressed. E-mail: benoit.lamarche@fsaa.ulaval.ca.
8
Abbreviations used: CAD, coronary artery disease; CVD, cardiovascular disease; GRADE:
Grading of Recommendations Assessment, Development, and Evaluation; IHD, ischemic
heart disease; MetS, metabolic syndrome; MOOSE, Meta-analysis Of Observational Study in
Epidemiology; T2D, type 2 diabetes; TFA, trans fatty acid.
Dairy products and cardiovascular health 1027
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number of cohort studies on this topic, the diversity of the
methods used to assess dairy fat intake, and the inconsistent
conclusions among studies (see Supplemental Information
for details).
Milk and risk of CVD. Despite the fact that the association
between milk consumption and CVD risk has been evaluated
in several meta-analyses of cohort studies (Supplemental
Table 6), the direction of this association cannot be estab-
lished with any confidence at this point because the estimates
of effects remain uncertain (very low quality of evidence;
Tabl e 2 ). The Supplemental Information provides detailed
information on this assessment. Future meta-analyses will
have to include data from all published studies to better re-
flect these associations, with particular consideration of
heterogeneity.
Cheese and risk of CVD. The search retrieved 2 meta-
analyses of the association between cheese consumption
and CVD risk (Supplemental Table 6). O’Sullivan et al. (15)
(RR: 1.00; 95% CI: 0.81, 1.24; no heterogeneity and no pub-
lication bias) and Alexander et al. (24) (RR: 0.89; 95% CI:
0.78, 1.01; no heterogeneity, publication bias not assessed)
reported no significant association between cheese intake
and CVD. One additional prospective study was retrieved,
which also reported no association between CVD risk
and the consumption of regular-fat or low-fat cheese (30)
(Supplemental Table 7). On the basis of data from 2 meta-
analyses that showed consistent results, there is high-quality
evidence that cheese intake is not associated with the risk of
CVD (Table 2).
Yogurt and risk of CVD. Alexander et al. (24) in their
meta-analysis reported no significant association between
yogurt consumption and CVD risk (RR: 0.93; 95% CI:
0.78, 1.12). Heterogeneity and publication bias were not
assessed. Of note, the authors did not identify references
of individual studies included in this particular analysis
and did not provide this information after being con-
tacted. In summary, evidence suggests that the association
between yogurt consumption and CVD risk is neutral,
and this assessment is based on moderate-quality evidence
(Table 2).
Fermented dairy and risk of CVD. The association be-
tween the consumption of fermented dairy and the risk of
CVD has not yet been meta-analyzed, to our knowledge.
In that context, the assessment of the association between
the consumption of fermented dairy and CVD risk is based
on very low-quality evidence and thus remains uncertain at
this point (Table 2). Additional information is available in
the Supplemental Information.
Dairy and risk of CVD—summary. The association be-
tween dairy consumption in various forms and CVD risk
has been evaluated in a limited number of meta-analyses
(Figure 1). Scientific evidence of moderate-to-high quality
indicates that intakes of total dairy, cheese, and yogurt are
neutral in terms of CVD risk. The quality of evidence relat-
ing high-fat dairy, low-fat dairy, milk, and fermented dairy
intake to CVD risk is considered to be very low and hence
no conclusion can be drawn with any confidence at this point
(Tabl e 2 ).
TABLE 1 List of meta-analyses included in this review and their quality score and funding source
First author, year (reference)
Quality
score,
1
% Funding source
Elwood et al., 2004 (5) 53 University of Wales College of Medicine and Bristol University, Food Standards Agency
Elwood et al., 2008 (6) 54 No funding
Elwood et al., 2010 (7) 54 No funding
Soedamah-Muthu et al., 2011 (8) 74 Dutch Dairy Association (unrestricted)
Tong et al., 2011 (9) 60 National Natural Science Foundation of China
Bendsen et al., 2011 (10) 80 Arla Food Amba
Ralston et al., 2012 (11) 69 National Health and Medical research Council of Australia
Soedamah-Muthu et al., 2012 (12) 71 Dutch Dairy Association (unrestricted), Global Dairy Platform
Aune et al., 2013 (13) 69 Liaison Committee between the Central Norway Regional Health Authority and the Norwegian
University of Science and Technology
Gao et al., 2013 (14) 80 National Natural Science Foundation of China
O‘Sullivan et al., 2013 (15) 83 National Health and Medical research Council of Australia
Chen et al., 2014 (16) 54 NIH
Chowdhury et al., 2014 (17) 100 British Heart Foundation, Medical Research Council, Cambridge National Institute for Health
Research Biomedical Research Centre, Gates Cambridge
Hu et al., 2014 (18) 71 Not indicated
Qin et al., 2015 (19) 64 Nestec Ltd. [Nestlé R&D (China) Ltd.]
de Souza et al., 2015 (20) 77 WHO
Larsson et al., 2015 (21) 66 Young Scholars Award Grant from the Strategic Research Area in Epidemiology, Karolinska Institutet
Chen et al., 2015 (22) 67 Yili Innovation Center, Inner Mongolia Yili Industrial Group Co., Ltd.
Kim and Je, 2016 (23) 67 Basic Science Research Program of the National Research Foundation of Korea, Ministry of Science,
Information and Communication Technology and Future Planning
Alexander et al., 2016 (24) 67 Dairy Research Institute
Gijsbers et al., 2016 (25) 73 Wageningen University
1
Quality score was calculated according to the MOOSE (Meta-analysis Of Observational Study in Epidemiology) checklist.
1028 Drouin-Chartier et al.
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CAD
Total dairy and risk of CAD. Soedamah-Muthu et al. (8)
in their meta-analysis reported no significant association be-
tween total dairy intake and the risk of CAD (RR: 1.02; 95%
CI: 0.93, 1.11; Supplemental Table 8). There was no evi-
dence of heterogeneity between studies and publication
bias was not assessed. Qin et al. (19) also reported no signif-
icant association between total dairy and CAD risk (RR:
0.94; 95% CI: 0.82, 1.07). There was significant heterogene-
ity between studies, but sensitivity analysis revealed little in-
fluence on the global interpretation of the data. There was
no evidence of publication bias in the meta-analysis by
Qin et al. (19). Finally, the recent meta-analysis by Alexander
et al. (24) reported no significant association between total
dairy intake and CAD risk (RR: 0.91; 95% CI: 0.80, 1.04).
There was significant heterogeneity between studies but no
evidence of publication bias. The search retrieved 1 small ad-
ditional prospective cohort study (31) in which total dairy in-
take and CAD were not associated (Supplemental Table 7). In
sum, there is high-quality evidence from 3 meta-analyses (8,
19, 24) that total dairy consumption is not associated with
CAD risk (Table 2 ).
Dairy fat and risk of CAD. In a dose-response meta-analysis
of 4 prospective cohort studies, Soedamah-Muthu et al. (8)
found no significant association between the intake of high-
fat dairy and CAD risk (RR: 1.04; 95% CI: 0.89, 1.21; Sup-
plemental Table 8) and between low-fat dairy intake and
total CAD risk (RR: 0.93; 95% CI: 0.74, 1.17). Potential
publication bias was not assessed, but there was no evi-
dence of heterogeneity between studies. The meta-analysis
by Qin et al. (19) came to the same conclusion for the analysis
of both regular- and high-fat
dairy and low-fat dairy. The
authors did not provide the
reference list specifictoeach
of those analyses in the pub-
lication or after being con-
tacted. In their meta-analysis,
Alexander et al. (24) reported
a neutral association between
high-fat dairy intake and CAD
risk (RR: 1.08; 95% CI: 0.93,
1.19) and an inverse association
between low-fat dairy intake
and CAD risk (RR: 0.90; 95%
CI: 0.82, 0.98). Heterogeneity
and publication bias were not
assessed.
Dairy fat contains naturally
occurring trans fatty acids (TFAs),
mostly vaccenic acid (trans-
18:1v-7). In 2011, Bendsen et al.
(10) published a meta-analysis
of 4 cohort studies that assessed
the association between the in-
take of TFAs from industrial
and ruminant origins and CAD risk. Intakes of TFAs from ru-
minants showed no significant association with CAD risk
(RR: 0.92; 95% CI: 0.76, 1.11). There was no evidence of
heterogeneity between studies. Results from the more recent
meta-analysis by de Souza et al. (20) also indicated that there
was no association between ruminant TFA intake and CAD
risk (RR: 0.93; 95% CI: 0.73, 1.18). In addition, de Souza
et al. reported null associations between intakes of the dairy-
specific FAs pentadecanoic acid (15:0; RR: 0.94; 95% CI: 0.44,
TABLE 2 Summary of the association between dairy product consumption and clinical
outcomes, with assessment of quality of evidence
1
CVD CAD Stroke Hypertension MetS T2D
Total dairy Neutral Neutral Favorable Favorable Favorable Favorable
Moderate High Moderate High Moderate Moderate
Regular- or high-fat dairy Uncertain Neutral Neutral Neutral Uncertain Neutral
Very low High Moderate Moderate Very low Moderate
Low-fat dairy Uncertain Neutral Favorable Favorable Uncertain Favorable
Very low High Moderate Moderate Very low High
Milk Uncertain Neutral Neutral Favorable Favorable Neutral
Very low Moderate Moderate Moderate Moderate Moderate
Cheese Neutral Neutral Favorable Neutral Uncertain Favorable
High Moderate Moderate High Very low Moderate
Yogurt Neutral Neutral Neutral Neutral Uncertain Favorable
Moderate Moderate Moderate Moderate Very low High
Fermented dairy Uncertain Uncertain Favorable Neutral Uncertain Neutral
Very low Very low Moderate Moderate Very low Moderate
1
Each of these associations is described in detail in the text. The association between dairy intake (any form) and the onset of
any clinical outcome is described as “unfavorable”(increased risk with dairy intake), “neutral”(no association between dairy
intake and risk), or “favorable”(reduced risk with increased intake of dairy). The quality of evidence (very low, low, moderate,
or high) is described by using the GRADE grading system as described in Supplemental Table 5. High-quality evidence de-
fines a situation in which “we are very confident that the true effect lies close to that of the estimate of the effect.”Moderate-
quality evidence indicates that “we are moderately confident in the effect estimate. The true effect is likely to be close to the
estimate of the effect, but there is a possibility that it is substantially different.”Low-quality evidence indicates that “our con-
fidence in the effect estimate is limited. The true effect may be substantially different from the estimate of the effect.”Very
low-quality evidence indicates that “we have very little confidence in the effect estimate. The true effect is likely to be sub-
stantially different from the estimate of the effect.”CAD, coronary artery disease; CVD, cardiovascular disease; GRADE, Grading
of Recommendations Assessment, Development, and Evaluation; MetS, metabolic syndrome; T2D, type 2 diabetes.
FIGURE 1 Forest plot of RRs from meta-analyses of prospective
cohort studies on the association between dairy intake and
cardiovascular disease risk, with their 95% CIs. Each symbol
represents data from an individual meta-analysis.
Dairy products and cardiovascular health 1029
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2.06) and heptadecanoic acid (17:0; RR: 0.92; 95% CI: 0.82,
1.03) and CAD risk. The authors reported significant het-
erogeneity between studies in the case of the association
between the intake of pentadecanoic acid specifically and
CAD risk, although publication bias was not evaluated
(20). Finally, Chowdhury et al. (17) in their meta-analysis
reported no significant association between plasma concen-
trations of pentadecanoic acid and CAD (RR: 0.94; 95% CI:
0.67, 1.32), whereas concentrations of heptadecanoic acid
were inversely associated with the risk of CAD (RR: 0.77;
95% CI: 0.63, 0.93). Plasma concentrations of palmitoleic
acid (cis-16:1v-7) showed no association with CAD risk
(RR: 0.96; 95% CI: 0.86, 1.08). Publication bias was not as-
sessed specifically for these associations, and there was moder-
ate heterogeneity between studies.
In summary, high-quality evidence from several meta-
analyses based on either self-reported dairy fat intake (8,
19) or on biomarkers of dairy fat intake (10, 17, 20) suggests
that high intakes of dairy fat are not associated with CAD
risk (Table 2). There is also high-quality evidence indicating
that the consumption of low-fat dairy products is not asso-
ciated with the risk of CAD.
Milk and risk of CAD. Elwood et al. (5–7) published 3
meta-analyses to assess the association between milk con-
sumption specifically and CAD risk (Supplemental Table
8). In 2004 (5), the authors reported no significant associa-
tion risk (RR: 0.84; 95% CI: 0.74, 1.03), whereas in 2008
they showed that high compared with low milk consump-
tion was associated with a reduced risk of CAD (RR: 0.84;
95% CI: 0.76, 0.93) (6). In their 2010 meta-analysis (7),
high compared with low consumption of milk was also as-
sociated with a significantly lower risk of CAD (RR: 0.92;
95% CI: 0.80, 0.99). There was no evidence of heterogeneity
between studies, and publication bias was not assessed in
any of the 3 meta-analyses, all of which had a low-quality
score on the basis of the MOOSE scale. Soedamah-Muthu
et al. (8) examined the dose-response relation between
milk intake and total CAD risk. Increased consumption of
milk showed no association with CAD risk (RR: 0.92; 95%
CI: 0.80, 0.99), without evidence of heterogeneity between
studies. Publication bias was not assessed. In their recent
meta-analysis, Alexander et al. (24) also reported no signifi-
cant association between milk consumption and CAD risk
(RR: 1.05; 95% CI: 0.95, 1.16). The authors did not provide
the list of studies included in this particular analysis and did
not provide this information after being contacted.
Overall, considering some degree of inconsistency among
available meta-analyses and based on our adapted GRADE cri-
teria (see Supplemental Methods), increased milk intake is sug-
gested to show no association with the risk of CAD, and this is
supported by moderate-quality evidence (Table 2 ). Whether
skimmed or low-fat milk is more favorably associated with
the risk of CAD than regular-fat milk has yet to be determined.
Cheese and risk of CAD. In 2010, Elwood et al. (7)
reported no significant association between cheese intake
and the risk of ischemic heart disease [(IHD); RR: 0.90;
95% CI: 0.79, 1.03; Supplemental Table 8]. However, results
are confounded by the fact that stroke was combined with
IHD as a study endpoint, which limits their interpretation.
Publication bias was not assessed, although there was no ev-
idence of heterogeneity between the 2 studies included in
the meta-analysis by Elwood et al. (7). Qin et al. (19) meta-
analyzed 7 prospective cohort studies on the association be-
tween cheese consumption and CAD risk. The authors did
not provide the list of studies included in this particular anal-
ysis. Cheese consumption tended to be inversely associated
with CAD risk (RR: 0.84; 95% CI: 0.74, 1.00). There was
no evidence of significant heterogeneity between studies
and no publication bias. Alexander et al. (24), on the basis
of 5 prospective cohort studies, concluded that there was a
significant inverse association between cheese consumption
and CAD risk (RR: 0.82; 95% CI: 0.72, 0.93).
In summary, cheese intake shows no significant associa-
tion with the risk of CAD (Table 2). The evidence support-
ing this observation is considered to be of moderate quality
because of the inconsistent results among meta-analyses.
There is, to date, no evidence that indicates that low-fat cheese
may be differentially associated with the risk of CAD compared
with regular-fat cheese.
Yogurt and risk of CAD. In the meta-analyses by Qin et al.
(19) and by Alexander et al. (24), yogurt consumption
showed no significant association with the risk of CAD
(Supplemental Table 8). Our search retrieved 2 additional
prospective cohort studies (31, 32), which may have been in-
cluded in the recent meta-analysis by Alexander et al. (24).
This remains unclear, because the authors did not provide
the list of studies included in their meta-analysis. In these in-
dividual prospective cohort studies, high compared with low
intakes of yogurt were also not associated with fatal or inci-
dent CAD risk (Supplemental Table 7).
The evidence that suggests a neutral association between
yogurt consumption and CAD risk appears to be consistent,
although existing meta-analyses lack important informa-
tion. For this reason, we suggest that this neutral association
between yogurt consumption and CAD risk is supported by
moderate-quality evidence (Table 2). The difference be-
tween regular-fat and low-fat yogurt in terms of CAD risk
cannot be determined at this point.
Fermented dairy and risk of CAD. The association be-
tween the consumption of fermented dairy and the risk of
CAD remains uncertain (Table 2), because only evidence
of insufficient quality is available (Supplemental Table 7).
Additional information is available in the Supplemental
Information.
Dairy products and CAD—summary. On the basis of
available meta-analyses and prospective cohort studies, there
is high-quality evidence that total dairy, high-fat dairy, and
low-fat dairy consumption shows no association with the
risk of CAD (Figure 2). The neutral association between
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intakes of milk, cheese, and yogurt and CAD risk is sup-
ported by evidence judged to be of moderate quality,
and the association between fermented dairy consump-
tion and CAD risk remains uncertain because of limited
evidence (Tabl e 2 ).
Stroke
Total dairy and risk of stroke. Hu et al. (18) assessed the
relation between total dairy intake and the risk of stroke
on the basis of data from 18 cohort studies (Supplemental
Table 9). Total dairy intake was inversely associated with
the risk of stroke (RR: 0.88; 95% CI: 0.82, 0.94). There
was no evidence of publication bias, but there was signifi-
cant heterogeneity between studies. However, the inverse as-
sociation between total dairy intake and the risk of stroke
remained significant when the 3 studies responsible for het-
erogeneity were excluded in sensitivity analyses. Qin et al.
(19) in their meta-analysis of 12 cohort studies also showed
that total dairy consumption was associated with a signifi-
cant reduction in stroke risk (RR: 0.87; 95% CI: 0.77, 0.99).
The authors reported significant heterogeneity between
studies as well as significant publication bias. Alexander et al.
(24) also recently reported an inverse association between total
dairy intake and stroke risk (RR: 0.91; 95% CI: 0.83, 0.99),
with again, significant heterogeneity between individual
studies. Of note, all prospective studies included in the
meta-analysis by Qin et al. (19) and Alexander et al. (24)
were also included in the meta-analysis by Hu et al. (18).
One additional cohort study (31) reported no association
between total dairy intake and stroke risk (Supplemental
Table 7). This study was very small compared with existing
data from previous meta-analyses and therefore unlikely to
have an impact on the reported pooled risk estimates from
existing meta-analyses.
In summary, the inverse association between total dairy
intake and the risk of stroke appears to be robust. However,
because results from the 3 meta-analyses are based on a rel-
atively homogeneous pool of cohort studies, we suggest that
this favorable association between intake of total dairy and
risk of stroke is based on moderate-quality evidence.
Dairy fat and risk of stroke. In the meta-analysis by Hu
et al. (18), no association was found between the intake of
high-fat dairy (as per the definition by the authors) and the
risk of stroke (RR: 0.96; 95% CI: 0.92, 1.01), whereas the in-
take of low-fat dairy products was associated with a 9% lower
risk of stroke (RR: 0.91; 95% CI: 0.85, 0.97; Supplemental
Table 9). There was no evidence of heterogeneity between
studies or of publication bias. Qin et al. (19) reached similar
conclusions for high-fat (RR: 0.95; 95% CI: 0.83, 1.08) and
low-fat (RR: 0.93; 95% CI: 0.88, 0.99) dairy. The authors did
not identify the individual cohort studies used in these spe-
cific analyses (19). However, we suspect that most of the
studies used by Qin et al. were included in the meta-analysis
by Hu et al., because this was the case when both groups as-
sessed total dairy. Alexander et al. (24) in their recent meta-
analysis reported inverse associations between both high-fat
dairy intake (RR: 0.91; 95% CI: 0.84, 0.99) and low-fat dairy
intake (RR: 0.90; 95% CI: 0.83, 0.96) and the risk of stroke.
In additional prospective cohort studies (31, 33), high in-
takes of dairy fat or low-fat dairy were not associated with
stroke risk (Supplemental Table 7).
In summary, because data from published meta-analyses
may be derived mostly from the same pool of cohort studies,
we conclude that there is moderate-quality evidence that the
intake of regular- and high-fat dairy is not associated with
the risk of stroke. On the other hand, the consumption of
low-fat dairy is favorably associated with stroke risk on the
basis of moderate-quality evidence (Table 2).
Milk and risk of stroke. Elwood et al. (5–7) published 3
meta-analyses relating milk consumption to stroke risk.
Articles published in 2004 (5), 2008 (6), and 2010 (7) all
reported a reduced risk of stroke associated with high com-
pared with low milk consumption (Supplemental Table 9).
Heterogeneity between studies was observed in the 2010
meta-analysis (7), and publication bias was not assessed in
any of the 3 meta-analyses. On the other hand, the dose-
response meta-analysis of Soedamah-Muthu et al. (8) showed
no association between milk consumption and the risk of
stroke (RR: 0.87; 95% CI: 0.72, 1.07). There was no evidence
of publication bias but significant heterogeneity between
studies was observed, with milk intake being associated
with a reduced risk of stroke among women but not among
men. The degree of adjustment for confounding factors also
appeared to attenuate the association between milk intake
and risk of stroke. Hu et al. (18) reported no significant as-
sociation between milk intake and the risk of stroke in their
meta-analysis (RR: 0.91; 95% CI: 0.82, 1.01). There was also
FIGURE 2 Forest plot of RRs from meta-analyses of
prospective cohort studies on the association between dairy
intake and coronary artery disease risk, with their 95% CIs. Each
symbol represents data from an individual meta-analysis. Arrows
indicate that the 95% CIs exceed the figure scale. R-TFA,
ruminant trans fatty acids.
Dairy products and cardiovascular health 1031
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significant heterogeneity between studies, but further analy-
sis that excluded the 3 studies responsible for this heteroge-
neity had no impact on the results. There was no evidence
of publication bias. Finally, Alexander et al. (24) recently
reported no significant association between milk consumption
and stroke risk (RR: 0.90; 95% CI: 0.79, 1.02), with significant
heterogeneity between studies. The authors did not provide the
list of references for this specific analysis.
In summary, 3 meta-analyses by the same group of au-
thors reported a favorable association between milk intake
and the risk of stroke, whereas meta-analyses conducted
by other groups, including 1 dose-response analysis, reported
null associations between milk intake and stroke risk. Thus,
milk consumption is not associated with the risk of stroke,
which is supported by moderate-quality evidence. There
is no evidence to date that skimmed or low-fat milk may
be more favorably associated with the risk of stroke than
regular-fat milk.
Cheese and risk of stroke. Elwood et al. (7) reported in
their meta-analysis no significant association between cheese
intake and the risk of IHD and stroke combined (RR: 0.90;
95% CI: 0.79, 1.03). There was significant heterogeneity be-
tween studies, and publication bias was not assessed. How-
ever, the combined assessment of IHD and stroke and the
limited number of cohort studies included (n=2)limitthe
generalizability of the results. Hu et al. (18) reported a small
but significantly lower risk of stroke with cheese consumption
(RR: 0.94; 95% CI: 0.89, 0.995). No evidence of publication
bias or heterogeneity between studies was found. Qin et al.
(19) also reported an inverse association between cheese con-
sumption and stroke risk (RR: 0.91, 95% CI: 0.84, 0.98).
Their meta-analysis revealed no significant heterogeneity
between studies and no publication bias. Alexander et al.
(24), on the basis of data from 4 prospective cohort studies,
reported an inverse association between cheese consumption
and stroke risk (RR: 0.87; 95% CI: 0.77, 0.99). It is unclear
how many cohort studies are common to these meta-analyses
because Qin et al. (19) did not provide references for their
analysis.
In summary, 3 meta-analyses with relatively large num-
bers of subjects concluded that cheese consumption is asso-
ciated with a reduced risk of stroke, whereas a meta-analysis
based on only 2 cohort studies with a low-quality score
reported a null association. As per our a priori–defined crite-
ria, we suggest that cheese intake is favorably associated with
the risk of stroke, and that this is supported by moderate-
quality evidence. More studies characterizing the association
between regular-fat and low-fat cheese and the risk of stroke
are needed.
Yogurt and risk of stroke. Qin et al. (19) meta-analyzed data
from prospective cohort studies and reported a null association
between yogurt consumption and the risk of stroke (RR: 0.98,
95% CI: 0.92, 1.06). Two additional cohort studies (31, 32)
also reported no significant association between yogurt con-
sumption and the risk of stroke (Supplemental Table 7).
The available meta-analysis has a relatively good quality score
and suggests that yogurt consumption is not associated with
theriskofstroke,andthisisbasedonmoderate-qualityevi-
dence (Tab l e 2 ).
Fermented dairy and risk of stroke. One meta-analysis
(18) showed that intake of fermented dairy was associated
with a reduced risk of stroke (RR: 0.80; 95% CI: 0.71,
0.89), without evidence of publication bias or heterogeneity
between studies (Supplemental Table 9). It must be stressed
that there were only 2 prospective cohort studies included
in this meta-analysis and its quality was rated as moderate
(Table 1). However, 2 recent prospective cohort studies reported
no association between fermented dairy and the risk of stroke
(31, 32) (Supplemental Table 7). The large number of indi-
viduals in these studies may change the risk estimates when
included in an updated meta-analysis.
On the basis of this finding, we suggest that there is
moderate-quality evidence that the consumption of fermented
dairy is associated with a reduced risk of stroke (Table 2). In-
deed, the meta-analysis available is based on only 3 prospec-
tive cohort studies and thus risk estimates may change with
future studies on this topic. The difference between regular-
fat and low- or no-fat yogurt intake in terms of stroke risk is
unknown.
Dairy and risk of stroke—summary. Although the con-
sumption of total dairy, low-fat dairy, cheese, and fermented
dairy may be associated with a reduced risk of stroke, intakes
of regular- and high-fat dairy, yogurt, and milk specifically
show no association with stroke risk (Table 2,Figure 3).
More research is warranted to further examine if the reduced-
fat version of a specific dairy product is more favorably as-
sociated with the risk of stroke than its regular-fat version.
Hypertension
Total dairy and risk of hypertension. In the meta-analysis
by Soedamah-Muthu et al. (12), for every 200-g/d increase
in total dairy intake, there was a significant 3% reduction
in the risk of hypertension (RR: 0.97; 95% CI: 0.95, 0.99;
Supplemental Table 10). There was no heterogeneity be-
tween studies, and no evidence of publication bias. In the
meta-analysis by Ralston et al. (11), total dairy intake was in-
versely associated with the risk of hypertension (RR: 0.87;
95% CI: 0.81, 0.94). There was no evidence of heterogeneity
between studies. Publication bias was not assessed. Four pro-
spective cohort studies were common to both meta-analyses.
Six prospective cohort studies were not included in these
meta-analyses (Supplemental Table 11). Four of these stud-
ies (34–37) reported a significant inverse association between
total dairy intake and the risk of hypertension, whereas the
other 2 reported no significant association (38, 39). Although
not all significant, the direction and magnitude of the hyper-
tension risk estimates with total dairy intake in these small
prospective cohort studies are comparable to numbers
reported in the meta-analyses by Soedamah-Muthu et al. (12)
and Ralston et al. (11). Data from these individual cohort
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studies are therefore unlikely to materially modify risk es-
timates from available meta-analyses, which are based on
combined sample sizes of >40,000 individuals.
Thus, data from available meta-analyses and prospective
cohort studies are fairly consistent in suggesting that total
dairy consumption is associated with a reduced risk of hy-
pertension (Tab l e 2 ). This assessment is based on high-quality
evidence according to the GRADE system.
Dairy fat and risk of hypertension. Soedamah-Muthu
et al. (12) in their meta-analysis (Supplemental Table 10) re-
ported no association between the consumption of high-fat
dairy and the risk of hypertension (RR: 0.99; 95% CI: 0.95,
1.03), whereas low-fat dairy intake was associated with a sig-
nificant reduction in the risk of hypertension (RR: 0.96; 95%
CI: 0.93, 0.99). Publication bias was not assessed, and results
were not found to be heterogeneous between studies for
either the low-fat or the high-fat dairy analysis. Similarly,
the consumption of high-fat dairy in the meta-analysis by
Ralston et al. (11) showed no association with the risk of hy-
pertension (RR: 1.00; 95% CI: 0.89, 1.11), whereas low-fat
dairy consumption was associated with a significant reduc-
tion in the risk of hypertension (RR: 0.84; 95% CI: 0.74,
0.95). There was significant heterogeneity between studies
but no mention of potential publication bias. All of the stud-
ies included in the meta-analysis by Ralston et al. (11) were
included in the meta-analysis by Soedamah-Muthu et al.
(12). The consumption of high-fat as well as low-fat dairy
foods has been associated with a reduced risk of elevated
blood pressure or hypertension in some (34, 37), but not
all (37, 40), additional prospective cohort studies, depend-
ing on how dairy products were categorized (Supplemental
Table 11).
Data from meta-analyses and additional prospective co-
hort studies suggest that the consumption of high-fat dairy
is not associated with the risk of hypertension or high blood
pressure, whereas low-fat dairy consumption may be associ-
ated with a reduced risk of hypertension (Table 2). Evidence
supporting this assessment is of moderate quality because
the 2 independent meta-analyses are based on essentially
the same pool of cohort studies.
Milk and risk of hypertension. In the only meta-analysis
available on this topic so far, Soedamah-Muthu et al. (12)
showed an inverse association between milk intake and the
risk of hypertension (RR: 0.96; 95% CI: 0.94, 0.98; Supple-
mental Table 10). Potential publication bias was not assessed,
but there was no apparent heterogeneity between studies. Ad-
ditional prospective cohort studies reported either significant
inverse associations (34, 39) or null associations (37, 38)
between milk consumption and the risk of hypertension
(Supplemental Table 11).
On the basis of results from 1 meta-analysis and from ad-
ditional prospective cohort studies, milk consumption may
be associated with a reduced risk of hypertension. The evi-
dence supporting this association is of moderate quality
(Tabl e 2 ). The extent to which reduced-fat milk may be
more favorably associated with a reduced risk of hyper-
tension than regular-fat milk is uncertain and needs fur-
ther consideration in future studies on this topic.
Cheese and risk of hypertension. In the meta-analysis by
Soedamah-Muthu et al. (12), cheese consumption showed
no significant association with the risk of hypertension
(RR: 1.00; 95% CI: 0.98, 1.03; Supplemental Table 10). No
evidence of heterogeneity was noted between studies, and
publication bias was not assessed. The meta-analysis by
Ralston et al. (11) came to similar conclusions (RR: 1.00; 95%
CI: 0.89, 1.12). The two meta-analyses had 4 cohort studies
in common. Other retrieved prospective cohort studies (34–
37, 39) reported no significant association between cheese
consumption and hypertension risk (Supplemental Table 11).
In sum, the 2 available meta-analyses and additional co-
hort studies were consistent in showing no significant asso-
ciation between cheese intake and the risk of hypertension.
Thus, there is high-quality evidence that cheese consump-
tion per se is not associated with the risk of hypertension
(Table 2). Whether the consumption of low-fat cheese is as-
sociated with more favorable blood pressure outcomes than
regular-fat cheese is uncertain.
Yogurt and risk of hypertension. Soedamah-Muthu et al.
(12) reported no significant association between yogurt con-
sumption (per 50 g/d) and the risk of hypertension (RR:
0.99; 95% CI: 0.96, 1.01; Supplemental Table 10) in their
meta-analysis of 5 prospective cohort studies. Results ap-
peared to be consistent between the different studies, and
publication bias was not assessed. Data from the prospective
CARDIA (Coronary Artery Risk Development in Young
Adults) (34) and SUN (Seguimiento University of Navarra)
FIGURE 3 Forest plot of RRs from meta-analyses of
prospective cohort studies on the association between dairy
intake and the risk of stroke, with their 95% CIs. Each symbol
represents data from an individual meta-analysis.
Dairy products and cardiovascular health 1033
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(40) cohorts are consistent with these findings in showing
no significant association between yogurt consumption and
hypertension risk (Supplemental Table 11). On the other
hand, an inverse association between yogurt consumption
and hypertension risk was reported in the Framingham Heart
Study (37) (RR: 0.95; 95% CI: 0.90, 0.99). In summary,
moderate-quality evidence suggests that yogurt consumption
is not associated with the risk of hypertension (Ta b l e 2 ).
Fermented dairy and risk of HTN. Soedamah-Muthu et al.
(12) pooled results from 4 prospective cohort studies
(Supplemental Table 10) and showed no significant asso-
ciation between the consumption of fermented dairy and
the risk of hypertension (RR: 0.99; 95% CI: 0.94, 1.04).
The only additional published study on this topic was con-
ducted by Wang et al. (37), who reported an inverse associa-
tion between the consumption of fermented dairy and the risk
of hypertension (Supplemental Table 11). This study has an
important weight (n= 2340) relative to data from the meta-
analysis by Soedamah-Muthu et al. (12) (n= 7641) and is likely
to modify pooled risk estimates. In this context, we suggest that
moderate-quality evidence supports a neutral association be-
tween the consumption of fermented dairy and the risk of hy-
pertension, with the need for further studies on the topic to
yield better quality evidence.
Dairy and risk of hypertension—summary. There is
moderate- to high-quality evidence that the consumption
of total dairy, low-fat dairy, and milk is associated with a
lower risk of hypertension (Figure 4,Ta b l e 2). There is
also moderate- to high-quality evidence that the consumption
of high-fat dairy (as per the authors’definition), cheese,
yogurt, and fermented dairy is not associated with the
risk of hypertension. Although the recommendation to
consume low-fat dairy foods in place of regular-fat pro-
ducts is partly consistent with data from blood pressure
studies, further investigation is warranted in this area to
assess whether the low-fat version of a dairy product (e.g.,
skimmed milk) is indeed more favorable than its regular-fat
version (whole milk) in terms of influencing blood pressure.
MetS
Two meta-analyses (22, 23) recently examined the association
between dairy consumption and the risk of MetS. Analyses
were based on data from a total of 9 individual prospective co-
hort studies, of which 3 used National Cholesterol Education
Program–Adult Treatment Panel III MetS criteria (35, 41, 42),
1 study used National Cholesterol Education Program–Adult
Treatment Panel III criteria with modified waist circumference
thresholds (38), 1 study used the insulin-resistance syndrome
criteria (34), 1 study used the American Heart Association cri-
teria (43), 2 studies used the International Diabetes Federation
criteria (44, 45), and 1 study used both American Heart Asso-
ciation and International Diabetes Federation criteria (40).
Total dairy and risk of MetS. Chen et al. (22) reported an
inverse association between total dairy consumption and the
risk of MetS (RR: 0.86; 95% CI: 0.79, 0.92; Supplemental
Table 12). There was no heterogeneity between studies,
and no evidence of publication bias. A dose-response analysis
revealed that each daily serving of dairy was associated with a
6% reduction in the risk of MetS (RR: 0.94; 95% CI: 0.90,
0.98). The meta-analysis by Kim and Je (23) also revealed
an inverse association between total dairy consumption and
the risk of MetS (RR: 0.85; 95% CI: 0.73, 0.98), with no evi-
dence of heterogeneity between studies or publication bias.
Similar results were obtained in their dose-response meta-
analysis, in which the risk of MetS was reduced by 12%/daily
serving of total dairy (RR: 88; 95% CI: 0.82, 0.95). The inclu-
sion of the cohort study by Sayón-Orea et al. (40), which was
based on yogurt intake only, appeared to have no impact on
the overall results reported by Kim and Je. The meta-analyses
by Chen et al. and Kim and Je both received moderate-quality
scores. One additional prospective cohort study suggested no
significant association between total dairy consumption
and the risk of MetS (46), although the risk estimate was
similar to the one reported in the meta-analyses (Supple-
mental Table 13).
In summary, data from 2 recent meta-analyses, which
were based on almost identical pools of prospective cohort
studies, suggest that total dairy consumption is inversely as-
sociated with the risk of MetS. Data from 1 additional small
prospective cohort study reported a similar association,
although it did not reach significance. According to the
adapted GRADE criteria, this indicates that the favorable as-
sociation between total dairy consumption and the risk of
MetS is supported by moderate-quality evidence (Tabl e 2 ).
Dairy fat and risk of MetS. To the best of our knowledge,
no meta-analysis has yet evaluated the association between
dairy fat and the risk of MetS, and data from available pro-
spective cohort have been inconsistent. Thus, in light of very
FIGURE 4 Forest plot of RRs from meta-analyses of
prospective cohort studies on the association between dairy
intake and the risk of hypertension, with their 95% CIs. Each
symbol represents data from an individual meta-analysis.
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low-quality evidence, the association between dairy fat and
the risk of MetS remains uncertain. A more detailed discussion
on this topic is available in the Supplemental Information.
Milk and risk of MetS. On the basis of pooled data from 3
prospective cohort studies, Chen et al. (22) reported an in-
verse association between milk consumption and the risk of
MetS (RR: 0.75; 95% CI: 0.63, 0.89; Supplemental Table 12).
There was no heterogeneity between studies, and publica-
tion bias was not evaluated specifically in this meta-analysis.
Additionally retrieved data from prospective cohort studies
showed either an inverse association (46) or no association
(46, 47) between milk consumption with various fat con-
tents and MetS risk (Supplemental Table 13).
The assessment of the association between milk consump-
tion and MetS risk is based on data from 1 meta-analysis of
only 4 prospective cohort studies (22), whereas data from ad-
ditionally retrieved prospective cohort studies are mixed. In
that context, we suggest that moderate-quality evidence sup-
ports a favorable association between milk consumption and
the risk of MetS (Tab le 2 ). The extent to which skimmed or
low-fat milk compared with regular-fat milk shows different
associations with the risk of MetS remains unclear and war-
rants further research.
Cheese and risk of MetS. To our knowledge, the association
between cheese consumption and the risk of MetS has not
been examined in a meta-analysis, and the limited number
of prospective cohort studies on this topic have yielded in-
conclusive evidence. The quality of evidence relating cheese
intake to MetS risk is considered to be very low and thus the
association remains uncertain (Table 2). Additional infor-
mation is provided in the Supplemental Information.
Yogurt and risk of MetS. There is a limited number of pro-
spective cohort studies and no meta-analysis on the associ-
ation between yogurt consumption and MetS risk. We judge
the quality of the evidence relating yogurt intake to the inci-
dence of MetS to be very low, and thus the association re-
mains uncertain. Additional information is available in the
Supplemental Information.
Fermented dairy and risk of MetS. To our knowledge,
there are currently no available studies on this topic.
Dairy and risk of MetS—summary. Overall, data on the
association between dairy intake and risk of MetS are limited
(Figure 5). Because total dairy and milk intake may be in-
versely associated with the risk of MetS (moderate-quality
evidence), evidence for other dairy foods are much limited
and of very low quality (Tab l e 2). Additional prospective co-
hort studies and meta-analyses are required to shed new light
on this topic.
T2D
Total dairy and risk of T2D. In the meta-analysis by
Elwood et al. (7), total dairy intake was associated with a sig-
nificantly reduced risk of T2D (RR: 0.85; 95% CI: 0.75, 0.96;
Supplemental Table 14). Results from the individual cohort
studies were relatively homogeneous, and there was no anal-
ysis of potential publication bias. Tong et al. (9) in their
meta-analysis also showed that the intake of dairy products
was inversely associated with the risk of T2D (RR: 0.86; 95%
CI: 0.79, 0.92). There was no heterogeneity between studies,
and no evidence of publication bias. Gao et al. (14) reported
an inverse association between total dairy intake and the risk
of T2D (RR: 0.89; 95% CI: 0.81, 0.98); and in a dose-
response analysis, the risk of T2D was reduced by 5% for
each 200-g/d increase in total dairy intake (RR: 0.95; 95%
CI: 0.92, 0.98). The authors indicated that there was signif-
icant heterogeneity between studies in both analyses but no
evidence of publication bias. Aune et al. (13) meta-analyzed
results from essentially the same pool of prospective cohort
studies, with a few exceptions, and reproduced the inverse
association between total intake of dairy products and the
risk of T2D (RR: 0.89; 95% CI: 0.82, 0.96; RR: 0.93 $400
g
21
$d
21
; 95% CI: 0.87, 0.99). The authors reported mod-
erate heterogeneity in results from the various cohort stud-
ies. Interestingly, the meta-analysis conducted by Chen et al.
(16), which was based on the largest sample size (n= 459,770),
showed no significant association between the total con-
sumption of dairy products and the risk of T2D (RR: 0.98;
95% CI: 0.96, 1.01). There was significant heterogeneity be-
tween studies, but no evidence of publication bias. Finally,
the most recent meta-analysis conducted by Gijsbers et al.
(25) also reported no association between total dairy con-
sumption and T2D risk (RR: 0.97; 95% CI: 0.95, 1.00).
Only 1 additional prospective cohort study was retrieved,
and no significant association was reported between total
dairy intake and T2D risk (48) (Supplemental Table 15).
In sum, results from available meta-analyses are not en-
tirely consistent, showing either favorable (4 meta-analyses)
or neutral (2 meta-analyses) associations between dairy in-
take and the risk of T2D, despite the fact that all were based
largely on the same pool of prospective cohort studies. Con-
sidering the weight of favorable meta-analyses compared
with neutral analyses, we suggest that there is moderate-
quality evidence supporting a favorable relation between total
dairy intake and incident T2D (Tab le 2 ). As emphasized
throughout this review, dairy products are heterogeneous,
and pooling them into a single analysis may lead to significant
heterogeneity, thus providing only partial perspectives on
their association with clinical outcomes. This appears to be
particularly the case for T2D.
Dairy fat and risk of T2D. Tong et al. (9) showed that the
consumption of high-fat dairy foods (as per the authors’def-
inition) was not associated with incident T2D (RR: 1.00; 95%
CI: 0.89, 1.10), whereas the consumption of low-fat dairy was
associated with a significantly reduced risk of T2D (RR: 0.82;
95% CI: 0.74, 0.90). Data from the Gao et al. (14) meta-analysis
are consistent with these findings. Indeed, a reduced risk
of T2D was associated with the intake of low-fat dairy (RR:
0.81; 95% CI: 0.74, 0.89) but not with the intake of high-
fat dairy (RR: 0.95; 95% CI: 0.85, 1.07). There was no evidence
Dairy products and cardiovascular health 1035
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of heterogeneity between studies. Dose-response analysis of
these cohort studies led to similar observations. Aune et al.
(13) reported no association between the intake of high-fat
dairy and incident T2D (RR: 0.96; 95% CI: 0.87, 1.06) in their
meta-analysis, without heterogeneity between studies. On the
other hand, a significant inverse association was reported for
low-fat dairy intake and the risk of T2D (RR: 0.83; 95% CI:
0.76, 0.90). Again, the dose-response analysis confirmed these
results. Recently, Gijsbers et al. (25) reported no association be-
tween T2D risk and the consumption of high-fat (RR: 0.97;
95% CI: 0.95, 1.00) or low-fat (RR: 0.98; 95% CI: 0.93, 1.04)
dairy. There was significant heterogeneity between individual
studies, but no evidence of publication bias. The association
between biomarkers of dairy fat and T2D incidence was as-
sessed in the meta-analysis by de Souza et al. (20). In this par-
ticular analysis, inverse associations were reported between
T2D risk and circulating concentrations of total ruminant
TFAs (RR: 0.58; 95% CI: 0.46, 0.74), pentadecanoic acid
(RR: 0.64; 95% CI: 0.46, 0.87) and heptadecanoic acid
(RR: 0.67; 95% CI: 0.63, 0.71). Of note, these analyses
were based on a limited number of prospective cohort studies
(from 2 to 5).
In summary, studies that ascertained the association be-
tween low-fat dairy consumption and the risk of T2D appear
to be relatively consistent, hence providing high-quality evi-
dence to support a favorable association. On the other
hand, data from cohort studies of self-reported high-fat dairy
intake and from analysis of biomarkers of dairy fat intake are
somehow at odds. Thus, we suggest there is moderate-quality
data to support the thesis that the consumption of high-fat
dairy has neutral effects on the risk of T2D (Tab l e 2 ). The ex-
tent to which further analyses of dairy fat intake with the use
of biomarkers, as in the meta-analysis by de Souza et al. (20),
will modify this perspective by confirming a favorable associ-
ation between dairy fat intake and the risk of T2D is of inter-
est in the future.
Milk and risk of T2D. Elwood et al. (6) in their meta-analysis
reported an inverse association between milk intake and
the risk of T2D (RR: 0.92; 95% CI: 0.86, 0.97; Supplemental
Table 14). The intake of whole milk showed no association
with the risk of T2D (RR: 0.95; 95% CI: 0.86, 1.05) in the
meta-analysis by Tong et al. (9). In the Gao et al. (14)
meta-analysis, high compared with low intakes of milk
were not significantly associated with a lower risk of T2D
(RR: 0.89; 95% CI: 0.78, 1.01). Analyses revealed moderate
heterogeneity between studies. A specificanalysisbasedon
milk-fat content indicated that the intake of low-fat milk
was associated with a significant reduction in the risk of
T2D (RR: 0.82; 95% CI: 0.69, 0.97), whereas the intake
of whole-fat milk was not (RR: 1.12; 95% CI: 0.99, 1.27)
(14). Aune et al. (13) reported no significant association be-
tween milk intake and T2D risk (RR: 0.87; 95% CI: 0.70,
1.07) on the basis of data from 7 prospective cohort studies.
In the most recent meta-analysis, Gijsbers et al. (25) reported
no significant association between total milk intake and T2D
risk (RR: 0.97; 95% CI: 0.93, 1.02). Significant heterogeneity
was observed, with no evidence of publication bias. The au-
thors reported similar associations with T2D risk for high-
fat (whole) milk (RR: 0.99; 95% CI: 0.88, 1.11) and low-fat
milk (RR: 1.01; 95% CI: 0.97, 1.05). In 2 additional prospec-
tive cohort studies (48, 49), milk consumption was not asso-
ciated with the risk of T2D (Supplemental Table 15).
In summary, 3 of the 4 available meta-analyses showed
that the intake of milk is not associated with a reduced
risk of T2D, whereas data from 1 meta-analysis suggested
a favorable inverse association between milk intake and
T2D risk. The meta-analyses by Gao et al. (14) and Aune
et al. (13) are based on very similar pools of studies. Con-
versely, the meta-analyses by Elwood et al. (6) and by
Tong et al. (9), both published before 2013, are based on
smaller pools of cohort studies. Considering the quality of
the meta-analyses available, their findings, and their similar-
ities, we suggest that there is moderate-quality evidence that
indicates that milk intake is not associated with the risk of
T2D, because it remains possible that risk estimates will be
modified once all prospective cohort studies are combined
(Tabl e 2 ). Further studies differentiating low-fat and regular-
fat milk with regard to the risk of T2D are also needed.
Cheese and T2D. According to the meta-analysis by Gao
et al. (14), cheese consumption is associated with a reduced
risk of T2D (RR: 0.82; 95% CI: 0.77, 0.87; Supplemental Table
14). Their dose-response analysis also revealed a significant in-
verse association between cheese intake (30 g/d) and incident
T2D (RR: 0.80; 95% CI: 0.69, 0.93). There was, however, sig-
nificant heterogeneity between studies. In the meta-analysis by
Auneetal.(13),cheeseconsumption,whenanalyzedonahigh-
compared with low-intake basis (RR: 0.91; 95% CI: 0.84, 0.98)
or by using a dose-response approach (RR: 0.92 per increment
of 50 g/d; 95% CI: 0.86, 0.99), was also associated with a lower
risk of T2D. In their 2016 meta-analysis, Gijsbers et al. (25) did
not confirm the inverse association between cheese consump-
tion and T2D risk (RR: 1.00 $10 g
21
$d
21
;95%CI:0.99,
FIGURE 5 Forest plot of RRs from meta-analyses of
prospective cohort studies on the association between dairy
intake and the risk of metabolic syndrome, with their 95% CIs.
Each symbol represents data from an individual meta-analysis.
1036 Drouin-Chartier et al.
by guest on November 18, 2016advances.nutrition.orgDownloaded from

1.02). Significant heterogeneity was present with an in-
creased risk of T2D in men with higher cheese consumption
(RR: 1.05 $10 g
21
$d
21
; 95% CI: 1.02, 1.09).
Because the available meta-analyses are based on the same
pool of prospective cohort studies, because of inconsistencies
among meta-analyses, and because of significant heterogeneity
between the various individual cohort studies, we suggest that
the reduced risk of T2D associated with cheese consumption is
supported by moderate-quality evidence (Tab l e 2 ). More stud-
ies are needed to substantiate if low-fat cheese is more favorably
associated with T2D risk than regular-fat cheese.
Yogurt and risk of T2D. Tong et al. (9) showed that high
compared with low yogurt consumption was associated
with a significantly lower risk of T2D (RR: 0.83; 95% CI:
0.74, 0.93). Heterogeneity between studies was not assessed,
but there was no evidence of publication bias. In their meta-
analysis, Gao et al. (14) also reported that high compared
with low intake of yogurt was inversely associated with incident
T2D (RR: 0.85; 95% CI: 0.75, 0.97). Analysis of the dose-
response association did not quite reach significance (RR:
0.91 $50 g
21
$d
21
;95%CI:0.82,1.00).Theauthorsreported
significant heterogeneity between studies. Finally, Aune et al.
(13) indicated that the intake of yogurt was associated with
a significantly reduced risk of T2D (RR: 0.86; 95% CI: 0.75,
0.98), which was not the case in the dose-response analysis
(RR: 0.78 $200 g
21
$d
21
; 95% CI: 0.60, 1.02). On the basis
of an updated meta-analysis of 14 studies, Chen et al. (16)
reported a favorable association between yogurt consumption
and the risk of T2D (RR: 0.82; 95% CI: 0.70, 0.96). There was
significant heterogeneity between studies, but no publication
bias. Finally, Gijsbers et al. (25) pooled data from 12 studies
and reported an inverse, nonlinear dose-response associa-
tion between yogurt consumption and T2D risk (RR: 0.94;
95% CI: 0.90, 0.97). In 2 additional prospective cohort stud-
ies not included in these meta-analyses, yogurt consumption
was also inversely associated with T2D risk (48, 50).
The 5 meta-analyses on the association between yogurt
intake and the risk of T2D reported consistent results.
Hence, we suggest that there is high-quality evidence that
supports an inverse association between the intake of yogurt
and the risk of T2D (Table 2). The extent to which low-fat
yogurt is more favorable that regular-fat yogurt in influencing
the risk of T2D is unknown.
Fermented dairy and risk of T2D. In the meta-analysis by
Gao et al. (14), there was no significant association between
intakes of fermented dairy products and the risk of T2D
(RR: 0.94; 95% CI: 0.75, 1.18). On the other hand, the intake
of fermented dairy was associated with a significant re-
duction in the risk of T2D (RR: 0.88; 95% CI: 0.79, 0.98)
in the meta-analysis by Aune et al. (13). Gijsbers et al. (25)
reported no association between fermented dairy product
consumption and the risk of T2D (RR for low-fat fermented
dairy: 0.98; 95% CI: 0.90, 1.06; RR for high-fat fermented
dairy: 0.92; 95% CI: 0.83, 1.03). No heterogeneity and no
publication were reported. In one additional prospective
cohort study (56), total fermented and regular- and high-fat
fermented dairy intakes were not associated with the risk of
T2D [RR (95% CI): 0.85 (0.68, 1.08) and 1.16 (0.91,1.49),
respectively], whereas the consumption of low-fat fermented
dairy was associated with a reduced risk of T2D (RR: 0.76;
95% CI: 0.60, 0.99; Supplemental Table 15).
In sum, the consumption of fermented dairy does not ap-
pear to be associated with the risk of T2D. This is based on
moderate-quality evidence, because the 3 meta-analyses avail-
able relied on almost the same pools of prospective cohort
studies (Ta b l e 2 ).
Dairy and T2D—summary. There is high-quality evidence
that intakes of low-fat dairy and yogurt are associated with a
reduced risk of T2D (Table 2,Figure 6). There is moderate-
quality evidence that suggests that intakes of total dairy and
cheese are also associated with a reduced risk of T2D. Finally,
the neutral association between intakes of high-fat dairy,
milk, and fermented dairy and T2D is supported by evidence
of high to moderate quality.
Interpretation and Conclusions
Investigating the impact of food products such as dairy on
health is highly challenging. There are obviously no ran-
domized controlled trials with hard endpoints available on
this topic, and such a trial is highly unlikely in the future.
Thus, the assessment of the association between dairy consump-
tion and clinical outcomes needs to rely primarily on data from
observational studies. This review used data from meta-analyses
in an attempt to draw the most reliable, evidence-based conclu-
sions relating dairy intake to cardiovascular-related clinical out-
comes. Ta b le 2 summarizes the quality of evidence from the
adapted GRADE scale as well as the direction of associations be-
tween dairy intake in various forms and clinical outcomes,
thereby answering the following key nutrition- and health-
related questions.
1. Is dairy consumption detrimentally, neutrally, or benefi-
cially associated with the risk of cardiovascular-related
clinical outcomes, including MetS and T2D?
First, there is no evidence that the consumption of any
form of dairy product is detrimentally associated with the
risk of any cardiovascular-related clinical outcome. In fact,
high-quality evidence supports favorable associations (i.e.,
decreased risk) between:
·total dairy intake and the risk of hypertension, and
·low-fat dairy and yogurt intake and the risk of T2D.
On the basis of the adapted GRADE criteria, we are confi-
dent that these associations are robust and hence unlikely
to be modified by further research.
Moreover, moderate-quality evidence suggests favorable
associations between:
·intakes of total dairy, low-fat dairy, cheese, and fermented
dairy products and the risk of stroke;
·intakes of low-fat dairy and milk and the risk of hypertension;
·intakes of total dairy and milk and the risk of MetS; and
·intakes of total dairy and cheese and the risk of T2D.
Dairy products and cardiovascular health 1037
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On the basis of the adapted GRADE criteria, these favorable
associations are very likely. However, future studies may mod-
ify risk estimates toward confirmed favorable associations or
toward the null.
Finally, there is high- to moderate-quality evidence that:
·consumption of total dairy, cheese, and yogurt is neutral in
terms of CVD risk;
·consumption of all forms of dairy, except for fermented, is
neutral in terms of CAD risk;
·consumption of regular- and high-fat dairy, milk, and yogurt is
neutral in terms of stroke risk;
·consumption of regular- and high-fat dairy, cheese, yogurt, and
fermented dairy is neutral in terms of risk of hypertension; and
·consumption of regular- and high-fat dairy, milk, and fer-
mented dairy is neutral in terms of risk T2D.
2. Is the recommendation to consume low-fat as opposed
to regular- and high-fat dairy supported by the existing
evidence?
First, there is no evidence from this extensive review that
the consumption of dairy fat or of regular- and high-fat dairy
is detrimental to cardiovascular-related clinical outcomes.
More specifically, the:
·consumption of regular- and high-fat dairy is neutral in terms
of risk of CAD, stroke, hypertension, and T2D, which is sup-
ported by high- to moderate-quality evidence;
·consumption of low-fat dairy is neutral in terms of CAD risk,
which is supported by high-quality evidence; and
·consumption of low-fat dairy is favorably associated with the
risk of stroke, hypertension, and T2D, which is supported by
high- to moderate-quality evidence.
Examining the association of dairy intake to health accord-
ing to fat content is tremendously challenging for several
reasons. In most epidemiologic studies, the “low-fat”termi-
nology generally referred to fat-reduced products such as
skimmed or low-fat milk (0–1% fat), nonfat yogurt (0%
fat), and low-fat cheese (15–20% fat). Inversely, whole milk
(3% fat) has been analyzed in population studies along with
regular-fat cheese (>30% fat) as regular- and high-fat dairy
products. The fat and nutrient profile is highly variable within
each of those categories. Grouping them into simplistic clas-
ses such as regular- and high-fat or low-fat may confound the
analysis of their association with clinical outcomes. A good
example of this pertains to cheese, which even in its low-fat
version is a product that is much higher in fat, and thus
that contributes more to SFA intake, than whole-fat milk.
Cheese intake is inversely associated with the risk of stroke
and T2D (supported by moderate-quality evidence), whereas
the intake of regular-fat dairy shows a neutral association with
these outcomes (moderate- to high-quality evidence). The use
of biomarkers of dairy fat intake provides a certain perspective
on the association between regular- and high-fat dairy and
health. However, it is limited by the fact that it does not allow
the study of the association between whole foods and health.
It is unclear in dietary guidelines if the recommendations
to consume low-fat dairy imply that individuals select the
low-fat version in place of the regular- and high-fat version
of a dairy product or choose an intrinsically low-fat dairy
(e.g., skimmed milk) instead of intrinsically high-fat dairy
(e.g., cheese). The first scenario represents a key research gap
that needs proper research. Indeed, high- or moderate-quality
evidence that shows that low-fat milk compared with whole-
milk or low-fat cheese compared with regular-fat cheese is bet-
ter for health is utterly lacking. The consumption of low-fat
dairy may provide some advantages with respect to the risk
of stroke, hypertension, and T2D, but there are currently no
data indicating that this is the case for each dairy product taken
individually. For the second scenario (e.g., choosing skimmed
milk instead of cheese), again, the evidence is weak because
in some instances (e.g., stroke, T2D), cheese consumption is
actually associated with a reduced risk. Replacing a solid
dairy such as cheese with a liquid dairy such as milk is a
much more complex dietary change than switching between
2 liquid foods or between 2 solid foods. Thus, more research
that addresses this particular scenario is also warranted, not
just from a health perspective but also from a dietary change
perspective. In the meantime, we hypothesize that the rec-
ommendation to focus on low-fat in place of regular- and
high-fat dairy products is a concept that may be not be fully
captured by the population, that such a concept may not re-
flect food choices that people make at the individual level,
and that such a recommendation is not based on the current
state of evidence.
As indicated above, additional studies are needed to ad-
dress the following key research gaps:
·to compare the impact of regular-fat dairy products with their
reduced-fat or skimmed versions on health outcomes;
FIGURE 6 Forest plot of RRs from meta-analyses of
prospective cohort studies on the association between dairy
intake and the risk of type 2 diabetes, with their 95% CIs. Each
symbol represents data from an individual meta-analysis. HF,
high-fat; LF, low-fat; R-TFA, ruminant trans fatty acids.
1038 Drouin-Chartier et al.
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·to assess the association between milk and fermented dairy
and the risk of CVD specifically, because these associations
are currently uncertain;
·to assess the association between cheese, yogurt, and fer-
mented dairy intakes specifically and the risk of MetS specifi-
cally, because these associations are currently uncertain; and
·to conduct higher quality meta-analyses, because 18 of the 21
available to date (Table 1) have been scored as being of mod-
erate quality or lower on the basis of the recognized MOOSE
grading system.
Assessing publication bias systematically in future meta-
analyses will also greatly enhance the quality of evidence.
This is identified as a major shortcoming in the existing
literature.
Some of the meta-analyses presented in this review have
revealed heterogeneity between prospective cohort studies.
Most studies have adjusted risk estimates for various covari-
ables, limiting the risk of confounding. However, one cannot
exclude the possibility of uncontrollable bias in large, prospec-
tive, epidemiologic cohort studies. Kratz et al. (51) stressed
that dietary assessment that uses FFQ in prospective cohort
studies may be influenced by the social value associated with
the food. In Western countries, high-fat dairy consumption
is much less prevalent than low-fat dairy consumption. This
has an obvious impact on the statistical power to measure as-
sociations with high-fat dairy. Kratz et al. also discussed the
impact of differences in bovine feeding practices between
countries, which affect the quality and composition of the
dairy fat. This has not been taken into account in existing pro-
spective cohort studies. Finally, the extent to which the associ-
ation between dairy intake and health outcomes is fully
independentofconcurrentvariationsinotherhealth-related
variables, such as diet, socioeconomic status, and other factors,
is unclear (51). Additional studies are therefore also needed
to assess the association between dairy intake and clinical
outcomes in various populations (obese compared with non-
obese, males compared with females, different geographical
areas) (16, 51).
In conclusion, this systematic review provides an in-
depth perspective on the association between dairy product
consumption and the risk of cardiovascular-related clinical
outcomes, including MetS and T2D. Although there are still
key research gaps to address, evidence suggests either a neutral
or a favorable association between dairy intake and cardiovas-
cular-related outcomes. These data are consistent with current
dietary guidelines, which place dairy as one of the pillars of
healthy eating. However, the review also emphasized that the
recommendationtofocusonlow-fatinplaceofregular-and
high-fat dairy is currently not evidence-based. Further research
is needed to specifically address this key research gap.
Acknowledgments
All authors read and approved the final manuscript.
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