SUPPLEMENT

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Milk and Dairy Product Consumption and
Cardiovascular Diseases: An Overview of
Systematic Reviews and Meta-Analyses
Javier Fontecha,1 Maria Visitación Calvo,1 Manuela Juarez,1 Angel Gil,2,3,4,5 and Vicente Martínez-Vizcaino6,7
1 Department of Bioactivity and Food Analysis, Food Lipid Biomarkers and Health Group, Institute of Food Science Research, CIAL (CSIC-UAM), Universidad
Autónoma de Madrid, Madrid, Spain; 2 Department of Biochemistry and Molecular Biology II, School of Pharmacy; 3 Institute of Nutrition and Food Technology
“José Mataix,” Biomedical Research Center, University of Granada, Granada, Spain; 4 Instituto de Investigación Biosanitaria ibs GRANADA, Complejo
Hospitalario Universitario de Granada, Granada, Spain; 5 CIBEROBN (CIBER Physiopathology of Obesity and Nutrition), Instituto de Salud Carlos III, Madrid,
Spain; 6 Health and Social Research Center, Universidad de Castilla-La Mancha, Cuenca, Spain; and 7 Facultad de Ciencias de la Salud, Universidad Autónoma
de Chile, Talca, Chile

ABSTRACT
Milk and dairy products containing milk fat are major food sources of saturated fatty acids, which have been linked to increased risk of cardiovascular-
related clinical outcomes such as cardiovascular disease (CVD), coronary heart disease (CHD), and stroke. Therefore, current recommendations by
health authorities advise consumption of low-fat or fat-free milk. Today, these recommendations are seriously questioned by meta-analyses of
both prospective cohort studies and randomized controlled trials (RCTs) reporting inconsistent results. The present study includes an overview of
systematic reviews and meta-analyses of follow-up studies, an overview of meta-analyses involving RCTs, and an update on meta-analyses of RCTs
(2013–2018) aiming to synthesize the evidence regarding the influence of dairy product consumption on the risk of major cardiovascular-related
outcomes and how various doses of different dairy products affect the responses, as well as on selected biomarkers of cardiovascular disease risk,
i.e., blood pressure and blood lipids. The search strategies for both designs were conducted in the MEDLINE, EMBASE, Cochrane Central Register of
Controlled Trials, Cochrane Database of Systematic Reviews, and Web of Science databases from their inception to April 2018. From the 31 full-text
articles retrieved for cohort studies, 17 met the eligibility criteria. The pooled risk ratio estimated for the association between the consumption of
different dairy products at different dose-responses and cardiovascular outcomes (CVD, CHD, and stroke) showed a statistically significant negative
association with RR values <1, or did not find evidence of significant association. The overview of 12 meta-analyses involving RCTs as well as the
updated meta-analyses of RCTs did not result in significant changes on risk biomarkers such as systolic and diastolic blood pressure and total
cholesterol and LDL cholesterol. Therefore, the present study states that the consumption of total dairy products, with either regular or low fat
content, does not adversely affect the risk of CVD. Adv Nutr 2019;10:S164–S189.

Keywords: milk consumption, dairy products, cardiovascular diseases, coronary heart disease, stroke

Introduction and varied diet within the context of a healthy lifestyle

Cardiovascular disease (CVD) is the leading cause of disabil-
ity and premature death throughout the world. An estimated
422.7 million cases of CVD and 17.92 million CVD deaths
occurred in 2015; ischemic heart disease (IHD) and stroke
were the first and second leading causes of CVD globally (1).
Hence, efforts to provide primary and secondary prevention
worldwide are required to reduce the burden of IHD, stroke,
and other related CVDs, such as peripheral arterial disease.
Risk factor modification, including improvement of di-
etary habits, can reduce clinical events in people with
established CVD, as well as in those who are at high
cardiovascular disease risk due to ≥1 risk factors. A balanced
is considered to be the most important CVD prevention
strategy (2).
Among the foods that feature in the Western diet and
other industrialized countries, regular milk as well as dairy
products have outstanding roles because the wide range
of nutrients (proteins, fats, carbohydrates, and minerals)
present in their composition play a fundamental part in the
human diet (3). However, because milk and dairy products
containing milk fat are major food sources of SFAs, they have
been linked to an increased risk of CVD derived from higher
blood concentrations of LDL cholesterol (4, 5). Therefore,
current recommendations by some health authorities and

S164 Copyright 
C American Society for Nutrition 2019. All rights reserved. Adv Nutr 2019;10:S164–S189; doi: https://doi.org/10.1093/advances/nmy099.
governments usually advise the consumption of low-fat or
fat-free milk and milk-derived products rather than regular-
fat dairy foods (6). Today, these recommendations are
seriously questioned by meta-analyses of both observational
studies and randomized controlled trials (RCTs) reporting
inconsistent results regarding the association between dairy
products and CVD risk regardless of dairy fat content (7).
Moreover, fermented dairy, such as yogurt or cheese, may
play a special protective role, possibly due to the influence of
the food matrix in the cardiometabolic response to saturated
fat (8–10). Likewise, recent studies consider milk to be one of
the most important sources of natural bioactive components
(11), which are otherwise difficult to obtain in diets with
limited use of dairy products.
In recent years, a number of reviews and meta-analyses
have focused on the influence of dairy product intake on
cardiovascular-related clinical outcomes, i.e., CVD, coronary
heart disease (CHD), and stroke (12–17). However, the
conclusions of these meta-analyses were not uniform. In ad-
dition, no meta-analysis of RCTs for major CVD events was
found. However, RCTs may provide important information
on causality, including the ability of dietary interventions
to affect biomarkers of future disease (18). Increased blood
pressure and LDL cholesterol, apart from other altered
plasma lipid concentrations, namely low HDL cholesterol,
high TGs, high apoB, and small, dense LDL, are considered
to be key targets for the prevention and treatment of
CVD (19, 20). Because atherosclerosis, vascular endothelial
dysfunction, and impaired coagulation are processes usually
linked to CVD, some inflammatory biomarkers, e.g., C-
reactive protein (CRP) and IL-6, as well as a number of
vessel adhesion molecules and coagulation factors have also
been related to an increased risk of CVD (21–23). A number
of meta-analyses and recent reviews have addressed how
dairy product consumption affects biomarkers of CVD (24–
35); the global evidence suggests that there are no harmful
effects, irrespective of the content of dairy fat, on a large
array of cardiometabolic variables, including lipid-related
risk factors, blood pressure, inflammation, insulin resistance,
and vascular function (36).
This supplement was sponsored by the Interprofessional Dairy Organization (INLAC), Spain.
The sponsor had no role in the design of the studies included in the supplement; in the
collection, analyses, or interpretation of the data; in the writing of the manuscripts; or in the
decision to publish the results. This study was partially funded by the University of Granada
Plan Propio de Investigación 2016, Excellence actions: Unit of Excellence on Exercise and
Health (UCEES), Plan Propio de Investigación 2018, Programa Contratos-Puente, the Junta de
Andalucía, Consejería de Conocimiento, Investigación y Universidades, and European Regional
Development Funds (ref. SOMM17/6107/UGR). Publication costs for this supplement were
defrayed in part by the payment of page charges. The opinions expressed in this publication
are those of the authors and are not attributable to the sponsors or the publisher, Editor, or
Editorial Board of Advances in Nutrition.
Author disclosures: JF, MVC, MJ, AG, and VM-V, no conflicts of interest.
Supplemental Tables 1–5 and Supplemental Figures 1–8 are available from the
“Supplementary data” link in the online posting of the article and from the same link in the
online table of contents at https://academic.oup.com/advances.
AG and VM-V contributed equally to this work.
Address correspondence to JF (e-mail: j.fontecha@csic.es).
Abbreviations used: CHD, coronary heart disease; CVD, cardiovascular disease; DBP, diastolic
blood pressure; IHD, ischemic heart disease; MI, myocardial infarction; RCT, randomized
controlled trial; SBP, systolic blood pressure.
The present overview of systematic reviews and meta-
analyses aimed to synthesize the evidence regarding the influ-
ence of dairy product consumption on major cardiovascular-
related outcomes and how different doses of specific dairy
products affect the responses. Likewise, we report an
overview of meta-analyses of RCTs summarizing the effects
of dairy consumption on selected cardiometabolic risk
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factors.
Methods
This overview of systematic reviews and meta-analyses was
registered through the International Prospective Register of
Systematic Reviews (PROSPERO) (CRD42018093723) and
reported according to the statements for Meta-analysis of
Observational Studies in Epidemiology (MOOSE) (37) and
Preferred Reporting Items for Systematic Reviews and Meta-
Analyses (PRISMA) (38). Likewise, it was guided by previous
reviews of reviews (39, 40) and the Cochrane Collaboration
Handbook recommendations (41). In addition, an updated
review was performed of RCTs and meta-analyses conducted
to investigate the effect of milk and other dairy products on
blood pressure and lipid biomarkers of cardiometabolic risk.
We did not attempt to investigate the effects on inflammation,
endothelial dysfunction, and coagulation factors, because
this has been specifically addressed in another article of the
present supplement on Role of Milk and Dairy Products
in Health and Prevention of Noncommunicable Chronic
Diseases: A Series of Systematic Reviews (23).
Search strategy
An electronic search strategy was conducted in the MED-
LINE, EMBASE, Cochrane Central Register of Controlled
Trials, Cochrane Database of Systematic Reviews, and Web
of Science databases from their inception to April 2018.
The following terms were combined to design the search
strategy: 1) “angina,” “athero,” “cardiac arrest,” “cardiac
death,” “cardiovascular,” “cardiovascular diseases,” CVD,
“cardiovascular mortality,” “cerebrovascular,” “cerebrovascu-
lar accident,” “coronary artery disease,” “coronary death,”
“coronary heart disease,” CHD, “death sudden,” “heart at-
tack,” “heart attacks,” “heart disease,” “heart diseases,” “heart
failure,” “ischemia,” “ischemic,” “myocardial infarction,”
“myocardial infarctions,” “stroke,” “strokes,” “sudden death,”
or “vascular diseases”; 2) dairy, milk, yogurt, cheese, kefir,
butter, or “dairy products”; and 3) review or meta (see Table
1, Supplementary Tables 1 and 2). In addition, reference
lists of identified systematic reviews and meta-analyses were
reviewed.
The literature search was independently performed by 2
reviewers (VM-V and JF), and disagreements were solved by
consensus or involving a third researcher (AG).
For the investigation of RCTs published from January,
2013 to August, 2018 related to dairy product consump-
tion and biomarkers of cardiometabolic risk we used the
following search equation for PUBMED (or its equivalent
for the other databases): [“dairy products”(All Fields) OR
Dairy products and cardiovascular disease S165
 TABLE 1 Characteristics of the meta-analyses included for cohort studies analyzing the effects of dairy consumption on major cardiovascular events1

S166
Risk of bias
Authors n Age, y Follow-up, y n (cases) Outcome observed Exposure observed RR (95% CI) I2 (%) (AMSTAR-2)
Alexander et al. (13)2 31 cohort studies 16–103 12–26 45,315 (NA) CVD Total dairy products3 0.88 (0.75, 1.04) 52.7 Good
(33 populations) Milk3 0.94 (0.86, 1.03) 38.1

Supplement
Cheese3 0.89 (0.78, 1.01) 13.0
Yogurt3 0.93 (0.78, 1.12) 43.4
183,020 (NA) CHD Total dairy products3 0.91 (0.80, 1.04) 52.8
High-fat dairy products3 1.05 (0.93, 1.19) 29.3
Low-fat dairy products3 0.90 (0.82, 0.98)∗ 0.0
<300 g total dairy products/d4 0.88 (0.80, 0.96)∗ 63.0
300–600 g total dairy products/d4 0.93 (0.85, 1.00) 51.6
>600 g total dairy products/d4 0.86 (0.79, 0.94)∗ 0.0
Milk3 1.05 (0.95, 1.16) 5.0
<244 g milk/d4 0.99 (0.86, 1.13) 0.0
244–488 g milk/d4 1.02 (0.93, 1.10) 0.0
>488 g milk/d4 0.98 (0.86, 1.12) 29.3
Cheese intake3 0.82 (0.72, 0.93)∗ 0.0
<18 g cheese/d4 1.00 (0.92, 1.07) 0.0
18–53 g cheese/d4 0.86 (0.75, 0.97)∗ 50.6
>53 g cheese/d4 0.92 (0.87, 0.97)∗ 0.0
Yogurt intake3 1.08 (0.91, 1.28) 41.7
286,474 (NA) Stroke Total dairy products3 0.91 (0.83, 0.99)∗ 44.5
High-fat dairy products3 0.91 (0.84, 0.99)∗ 0.0
Low-fat dairy products3 0.90 (0.83, 0.96)∗ 0.0
<300 g total dairy products/d4 0.92 (0.89, 0.96)∗ 0.0
>300 g total dairy products/d4 0.91 (0.88, 0.95)∗ 0.0
Milk3 0.90 (0.79, 1.02) 79.6
<244 g milk/d4 0.95 (0.86, 1.04) 76.7
244–488 g milk/d4 0.98 (0.90, 1.06) 38.2
>488 g milk/d4 1.01 (0.92, 1.11) 44.9
Cheese intake3 0.87 (0.77, 0.99)∗ 33.5
<18 g cheese/d4 1.00 (0.92, 1.07) 0.0
18–53 g cheese/d4 0.86 (0.75, 0.97)∗ 50.6
>53 g cheese/d4 0.92 (0.87, 0.97)∗ 0.0
NA (NA) Ischemic stroke Total dairy products3 0.96 (0.76, 1.20) 73.2
Milk 0.93 (0.81, 1.06) 75.6
NA (NA) Hemorrhagic stroke Milk3 0.93 (0.69, 1.25) 86.6
Bechthold et al. (42) 24 cohort studies 20–100 5–26 351,683 (14,614) CHD Total dairy products3 0.99 (0.92, 1.07) 59.0 Excellent
(27 populations) 200 g total dairy products/d4 0.99 (0.96, 1.02) 55.0
High-fat dairy products3 1.01 (0.96, 1.06) 9.0
Low-fat dairy products3 0.96 (0.90, 1.03) 42.0
419,782 (19,207) Stroke Total dairy products3 0.96 (0.90, 1.01) 43.0
200 g total dairy products/d4 0.98 (0.96, 1.00) 50.0
High-fat dairy products3 0.93 (0.87, 0.99)∗ 32.0
Low-fat dairy products3 0.97 (0.91, 1.04) 39.0
Ischemic stroke Total dairy products3 0.95 (0.88, 1.01) 26.0
Hemorrhagic stroke Total dairy products3 1.01 (0.84, 1.21) 20.0
85,372 (4057) Heart failure Total dairy products3 1.00 (0.90, 1.10) 67.0
200 g total dairy products/d4 1.08 (1.01, 1.15) NA

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 TABLE 1 (Continued)

Risk of bias
Authors n Age, y Follow-up, y n (cases) Outcome observed Exposure observed RR (95% CI) I2 (%) (AMSTAR-2)
Chen et al. (16) 15 cohort studies 16–93 8–16 102,013 (8076) CVD Cheese3 0.90 (0.82, 0.99)∗ 0.0 Very good
(15 populations) High-fat cheese3 0.74 (0.44, 1.24) 67.0
Low-fat cheese3 1.00 (0.77, 1.29) NA
50 g cheese/d4 0.92 (0.83, 1.02) 16.9
121,226 (7631) CHD Cheese3 0.86 (0.77, 0.96)∗ 14.9
High-fat cheese3 0.83 (0.68, 1.01) NA
Low-fat cheese3 1.13 (0.63, 2.05) 90.5
50 g cheese/d4 0.90 (0.84, 0.95)∗ 0.0
257,069 (10,449) Stroke Cheese3 0.90 (0.84, 0.97)∗ 0.0
50 g cheese/d4 0.94 (0.84, 1.04) 63.7
Elwood et al. (43) 10 cohort studies and 16–79 8–28 401,682 (8850) CVD Milk intake3 0.84 (0.78, 0.90)∗ NA Acceptable
2 case control studies 89,598 (4820) IHD Milk intake3 0.87 (0.74, 1.03) NA
(12 populations) 320,361 (4030) Stroke Milk intake3 0.83 (0.77, 0.90)∗ NA
Elwood et al. (44) 15 cohort studies and NA 8–28 239,317 (5835) IHD Total dairy products3 0.84 (0.76, 0.93)∗ NA Acceptable
4 case control studies 414,097 (14,358) Stroke Total dairy products3 0.79 (0.75, 0.82)∗ NA
(14 populations) 2350 (1011) MI Total dairy products3 0.83 (0.66, 0.99)∗ NA
Elwood et al. (45) 25 cohort studies NA 5–68 64,322 (10,121) CVD Butter3 0.93 (0.84, 1.02) NA Acceptable
(25 populations) 116,828 (11,019) Cheese3 1.32 (0.49, 3.56) NA
379,503 (10,059) IHD Total dairy products3 0.92 (0.80, 0.99)∗ NA
587,690 (9725) Ischemic stroke Total dairy products3 0.79 (0.68, 0.91)∗ NA
388,371 (5946) Hemorrhagic stroke Total dairy products3 0.75 (0.60, 0.94)∗ NA
121,469 (484) Subarachnoid bleeds Total dairy products intake3 0.65 (0.32, 1.31) NA
Gholami et al. (15) 27 cohort studies 8–97 5–65 140,851 (8648) CVD (fatal and nonfatal) Total dairy products3 0.90 (0.81, 0.99)∗ 55.9 Very good
(31 populations) 55,421 (NA) CVD incidence Total dairy products3 0.93 (0.84, 1.04) 32.5
85,430 (NA) CVD mortality Total dairy products3 0.87 (0.74, 1.03) 64.6
471,970 (11,806) CHD (fatal and nonfatal) Total dairy products3 0.99 (0.92, 1.06) 51.6
High-fat dairy products3 0.98 (0.94, 1.01) 2.4
Low-fat dairy products3 1.01 (0.94, 1.09) 62.6
190,494 (7787) CHD incidence Total dairy products3 0.97 (0.90, 1.04) 44.9
281,476 (4019) CHD mortality Total dairy products3 1.03 (0.88, 1.21) 58.1
764,917 (29,300) Stroke (fatal and nonfatal) Total dairy products3 0.88 (0.82, 0.95)∗ 63.1
High-fat dairy products3 0.95 (0.91, 1.00) 0.0
Low-fat dairy products3 0.94 (0.90, 0.98)∗ 0.0
297,446 (13,979) Stroke incidence Total dairy products3 0.96 (0.88, 1.04) 49.7
467,471 (15,321) Stroke mortality Total dairy products3 0.80 (0.76, 0.83)∗ 0.0
Gholami et al. (46) 15 cohort studies 8–83 10–65 135,126 (8011) CHD Total dairy products3 0.97 (0.93, 1.02) 20.7 Very good
(16 populations) Milk3 1.05 (0.96, 1.15) 0.0
Butter3 0.99 (0.89, 1.11) 21.2
Cheese3 0.90 (0.81, 1.01) 47.4
Cream3 0.96 (0.87, 1.06) 0.0
496,943 (23,477) Stroke Total dairy products3 0.93 (0.88, 0.98)∗ 54.2
Milk3 0.91 (0.81, 1.01) 71.4
Butter3 0.95 (0.85, 1.07) 0.0
Cheese3 0.93 (0.88, 0.99)∗ 0.0
Cream3 0.97 (0.88, 1.06) 0.0

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S168
TABLE 1 (Continued)

Risk of bias
Authors n Age, y Follow-up, y n (cases) Outcome observed Exposure observed RR (95% CI) I2 (%) (AMSTAR-2)

Supplement
de Goede et al. (47) 18 cohort studies 30–83 8–26 336,118 (12,425) Stroke 200 g total dairy products/d4 0.99 (0.96, 1.02) 65.6 Very good
(20 populations) 200 g fermented dairy products/d4 0.91 (0.82, 1.01) 64.5
200 g high-fat dairy products/d4 0.96 (0.93, 0.99)∗ 0.0
200 g low-fat dairy products/d4 0.97 (0.95, 0.99)∗ 0.0
200 g milk/d4 0.93 (0.88, 0.98)∗ 86.0
200 g high-fat milk/d4 1.04 (1.02, 1.06) 0.0
200 g low-fat milk/d4 0.96 (0.90, 1.03) 68.2
10 g butter/d4 1.00 (0.99, 1.01) 0.0
40 g cheese/d4 0.97 (0.94, 1.01) 31.2
100 g yogurt/d4 1.02 (0.90, 1.17) 47.8
158,595 (6440) Ischemic stroke 200 g total dairy products/d4 1.00 (0.96, 1.04) 83.6
200 g milk/d4 0.95 (0.89, 1.01) 67.6
158,595 (1237) Hemorrhagic stroke 200 g total dairy products/d4 1.02 (0.98, 1.06) 94.4
200 g milk/d4 0.90 (0.74, 1.09) 0.0
87,576 (1652) Stroke mortality 200 g total dairy products/d4 0.97 (0.85, 1.11) 65.1
200 g fermented dairy products/d4 0.80 (0.67, 0.95)∗ 0.0
200 g milk/d4 0.88 (0.81, 0.96)∗ 65.3
Guo et al. (14) 26 cohort studies 34–67 5–25 76,207 (5525) CVD 200 g total dairy products/d4 0.97 (0.91, 1.02) 59.9 Very good
(28 populations) 200 g fermented dairy products/d4 0.98 (0.97, 0.99)∗ 87.5
200 g high-fat dairy products/d4 0.93 (0.84, 1.03) 37.4
200 g low-fat dairy products/d4 0.98 (0.95, 1.01) 0.0
244 g milk/d4 1.01 (0.93, 1.10) 92.4
10 g cheese/d4 0.98 (0.95, 1.00) 82.6
50 g yogurt/d4 1.03 (0.97, 1.09) 0.0
330,350 (8298) CHD 200 g total dairy products/d4 0.99 (0.96, 1.02) 38.9
200 g fermented dairy products/d4 0.99 (0.98, 1.01) 44.6
200 g high-fat dairy products/d4 0.99 (0.93, 1.05) 22.9
200 g low-fat dairy products/d4 1.00 (0.97, 1.03) 27.3
244 g milk/d4 1.01 (0.96, 1.06) 45.5
10 g cheese/d4 0.99 (0.97, 1.02) 40.3
50 g yogurt/d4 1.03 (0.97, 1.09) 0.0
Hu et al. (48) 15 cohort studies 30–103 10–65 764,635 (28,138) Stroke (fatal and nonfatal) Total dairy products3 0.88 (0.82, 0.94)∗ 61.8 Good
(18 populations) High-fat dairy products3 0.96 (0.92, 1.01) 0.0
Low-fat dairy products3 0.91 (0.85, 0.97)∗ 41.6
Milk3 0.91 (0.82, 1.01) 74.4
Fermented milk3 0.80 (0.71, 0.89)∗ 0.0
Nonfermented milk3 1.02 (0.89, 1.17) 0.0
Butter3 0.95 (0.85, 1.07) 0.0
Cheese3 0.94 (0.89, 1.00) 0.0
Cream3 0.97 (0.88, 1.06) 0.0
293,320 (13,415) Stroke incidence Total dairy products3 0.95 (0.87, 1.03) 50.9
471,315 (14,723) Stroke mortality Total dairy products3 0.80 (0.76, 0.84)∗ 0.0
456,420 (12,439) Ischemic stroke Total dairy products3 0.92 (0.82, 1.03) 63.3
451,847 (6625) Hemorrhagic stroke Total dairy products3 0.96 (0.73, 1.25) 82.7

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 TABLE 1 (Continued)

Risk of bias
Authors n Age, y Follow-up, y n (cases) Outcome observed Exposure observed RR (95% CI) I2 (%) (AMSTAR-2)
Larsson et al. (49) 4 cohort studies 25–79 11–25 209,046 (49,955) CVD mortality Nonfermented milk3 NA 93.0 Acceptable
(6 populations)
Mullie et al. (50) 15 cohort studies 34–74 10–25 403,776 (37,049) CHD (fatal and nonfatal) 200 g milk/d4 1.01 (0.98, 1.05) 16.0 Good
(15 populations) 564,717 (39,352) Stroke (fatal and nonfatal) 200 g milk/d4 0.91 (0.82, 1.02) 92.0
Pimpin et al. (51) 4 cohort studies 55–70.6 10–16.2 175,612 (9783) Any CVD Butter3 1.00 (0.98, 1.02) 0.0 Very good
(5 populations) 149,056 (4484) CHD Butter3 0.99 (0.96, 1.03) 0.0
173,853 (5299) Stroke Butter3 1.01 (0.98, 1.03) 0.0
NA Total CVD Butter3 0.99 (0.96, 1.02) 0.0
Qin et al. (12) 22 cohort studies 21–83 8–26.2 91,057 (7641) CVD Total dairy products3 0.88 (0.81, 0.96)∗ 29.6 Very good
(NA) 504,803 (21,801) Stroke Total dairy products3 0.87 (0.77, 0.99)∗ 69.8
High-fat dairy products3 0.95 (0.83, 1.08) 72.1
Low-fat dairy products3 0.93 (0.88, 0.99)∗ 20.0
Yogurt3 0.98 (0.92, 1.06) 0.0
Cheese3 0.91 (0.84, 0.98)∗ 0.0
Butter3 0.94 (0.84, 1.06) 12.9
253,260 (8792) CHD Total dairy products3 0.94 (0.82, 1.07) 58.5
High-fat dairy products3 1.08 (0.99, 1.17) 0.0
Low-fat dairy products3 1.02 (0.92, 1.14) 33.5
Yogurt3 1.06 (0.90, 1.34) 42.9
Cheese3 0.84 (0.71, 1.00) 31.8
Butter3 1.02 (0.88, 1.20) 30.7
Soedamah-Muthu et 17 cohort studies 34–80 5–25 13,518 (2283) CVD 200 mL milk/d4 0.94 (0.89, 0.99)∗ 0.0 Very good
al. (52) (NA) 259,162 (4391) CHD 200 mL milk/d4 1.00 (0.96, 1.04) 26.9
Total dairy product intake3 1.02 (0.93, 1.11) 26.2
Total high-fat dairy3 1.04 (0.89, 1.21) 0.0
Total low-fat dairy3 0.93 (0.74, 1.17) 55.7
375,381 (15,554) Stroke Total milk3 0.87 (0.72, 1.07) 94.6
Wu and Sun (53) 9 cohort studies 21–55 10.2–17.3 291,236 (14,776) Developing CVD Yogurt3 0.99 (0.96, 1.11) 52.0 Very good
(9 populations) 77,510 (4381) CHD Yogurt3 1.04 (0.95, 1.15) 36.0
225,141 (7875) Stroke Yogurt3 1.02 (0.92, 1.13) 58.0
1∗
P < 0.05. CHD, coronary heart disease; CVD, cardiovascular disease; NA, not available.
2
Servings per day were converted into grams per day (a single serving of milk as 244 g, 1 serving of cheese as 35 g, and 1 serving of total dairy, high-fat dairy, and low-fat dairy as 200 g).
3
High compared with low intake.
4
Per each increment of the cited dairy products.

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“milk”(All Fields) OR “cheese”(All Fields) OR “yogurt”(All
Fields) OR “yoghurt”(All Fields) OR “fermented milk”(All
Fields)] AND [“blood lipids”(All Fields) OR “blood pres-
sure”(All Fields) OR “cholesterol”(All Fields) OR “LDL-
cholesterol”(All Fields) OR “HDL-cholesterol”(All Fields)
OR “triglycerides”(All Fields) OR “low-density lipopro-
tein”(All Fields) OR “high-density lipoprotein”(All Fields)
OR “non high-density lipoprotein cholesterol”(All Fields)
OR “apolipoprotein B”(All Fields) OR “apolipoprotein A-
I”(All Fields) OR “small dense LDL”(All Fields) OR “LDL
particle size”(All Fields) OR “Lp(a)”(All Fields) OR “glu-
cose”(All Fields) OR “insulin”(All Fields) OR “insulin re-
sistance”(All Fields) OR “HOMA”(All Fields) OR “vascu-
lar function”(All Fields) OR “fibrinogen”(All Fields) OR
“flow mediated dilation”(All Fields) OR “peripheral arte-
rial tone”(All Fields) OR “adhesion molecules”(All Fields)]
NOT [“human milk”(All Fields) OR “infant formula”(All
Fields) OR “milk formula”(All Fields)] AND {Random-
ized Controlled Trial[ptyp] AND [“2013/01/01”(PDAT):
“2018/08/31”(PDAT)]}. A similar strategy was applied to
screen the meta-analyses of RCTs for biomarkers of car-
diometabolic risk associated with milk and dairy product
consumption.
The literature search for RCTs and RCT meta-analyses
was independently performed by 2 reviewers (JF and AG),
and disagreements were solved by consensus involving a
third researcher (VM-V).
Study selection
Only systematic reviews and meta-analyses addressing the
relation between dairy product consumption and cardio-
vascular outcomes were considered. Meta-analyses were
included if they: 1) included longitudinal studies or data from
longitudinal studies that could be isolated or extracted (in
case they also included RCTs or cross-sectional studies), and
2) were written in English or Spanish. Meta-analyses not
following systematic review methodology were excluded.
For the study of RCTs related to dairy product consump-
tion and biomarkers of cardiometabolic risk, prospective,
parallel, and crossover designs were considered. Studies
had to administer dietary supplementation or a specific
diet containing dairy products. However, those studies that
used dietary recommendations or self-reporting alone were
excluded. Studies were also excluded if a supplement that
could potentially confound the effects of the milk or the dairy
product was administered.
Search and data extraction
Observational cohort studies and major cardiovascular
outcomes.
The main characteristics of the selected studies were summa-
rized in an ad hoc table, including information regarding the
1) first author and year of publication, 2) number of studies
included, 3) length of follow-up, 4) sample characteristics
(age distribution, number of subjects, and number of cases),
5) cardiovascular outcome observed, 6) type of dairy product
assessed, 7) risk ratio estimations, 8) heterogeneity reported
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[I2 (%)], and 9) AMSTAR 2 risk of bias value. In addition, the
longitudinal studies included in each meta-analysis and the
covariates included in their analysis were extracted.
From the 31 full-text articles retrieved, 17 studies met
the eligibility criteria (Figure 1). These meta-analyses quan-
tified the risk of the association between dairy product
consumption and cardiovascular outcomes. The reports were
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published between 2004 and 2017 and provided data from 4–
31 cohort studies and from 2–4 case control studies (Table
1). From the 17 systematic reviews and meta-analyses in
which risk of bias was evaluated using the AMSTAR 2 tool
(Supplemental Table 2), 8 of them were assessed as NOT in
item 9, which addresses whether the authors have adequately
evaluated the risk of bias of the included studies. Among
the causes of this negative assessment, it is noted that most
meta-analyses did not describe in depth the influence of the
confounders and effect modification variables.
The sample sizes of the included studies ranged from
2350 to 764,917 participants, and participants’ age ranged
from 8 to 103 y. These participants were followed for
between 5 and 83 y. The main cardiovascular outcomes
included in the meta-analyses were incidence and mortality
of CVD, CHD, and stroke. In addition, some studies reported
risk of IHD, myocardial infarction (MI), heart failure, and
ischemic and hemorrhagic stroke. The maximum number of
cardiovascular events, including fatal and nonfatal outcomes,
was 11,019 for CVD, 37,049 for CHD, and 39,352 for stroke.
Eleven studies reported information regarding total dairy
product consumption, 9 distinguished between regular-fat
and low-fat dairy products (12–16, 42, 47, 48, 52), and 2 (14,
47) included information regarding fermented dairy product
consumption. Furthermore, 9 studies reported information
regarding milk consumption (13, 14, 44, 46–50, 52), 2
regarding high-fat and low-fat milk consumption (48, 49),
2 regarding nonfermented milk consumption (48, 49), and
1 regarding fermented milk consumption (48). In addition,
cheese, yogurt, butter, and cream consumption were included
as exposures by other studies (12–14, 16, 43, 46–48, 51,
53). The heterogeneity reported in the meta-analyses, as
measured by I2 , varied from 0% to 94.6%.
From the total of 76 original cohort and case control
studies, no single one was included in all of the systematic
reviews and meta-analyses included in this overview and the
covariates used in their analyses varied across the original
studies, with demographic variables and health behaviors the
most commonly used (Supplementary Table 1).
RCTs and biomarkers of cardiometabolic risk.
The studies included the administration of milk or dairy
products, individually or in combination, allowing for the
investigation of the effects of the milk or dairy products.
There were no restrictions regarding dosage or dosing
regimen. The following primary outcomes were considered
for the inclusion of the studies: systolic blood pressure
(SBP), diastolic blood pressure (DBP), and plasma lipids
(total cholesterol, LDL cholesterol, HDL cholesterol, and

FIGURE 1 PRISMA flow diagram for the research of meta-analyses of cohort studies addressing the effects of the consumption of dairy
products and major events of cardiovascular diseases.
TGs). Other outcomes including inflammatory, endothelial
dysfunction, and coagulation factors have been reported
separately in another article of the present supplement (23).
As for the observational studies, the main characteristics
of the selected meta-analyses involving RCTs are summa-
rized in Tables 2 and 3. Likewise, the characteristics of the
RCTs included in the updated meta-analysis (2013–2018) are
shown in Table 4.
From the 15 full-text meta-analyses retrieved, 12 stud-
ies met the eligibility criteria (Supplemental Figure 1).
Likewise, from the 30 RCT studies retrieved from 2013 to
2018, only 12 met the inclusion criteria for the updated
meta-analysis study (Supplemental Figure 2). These meta-
analyses quantified the risk of consumption of dairy products
on blood lipids and blood pressure biomarkers.
Risk of bias and certainty of evidence
Observational cohort studies and major cardiovascular
outcomes.
The AMSTAR 2 tool (54) was used to evaluate the quality
of the included systematic reviews and meta-analyses. This
tool includes 16 criteria, each referring to a relevant method-
ological aspect of the study (e.g., there should be a previous
study protocol, ≥2 independent data extractors, a consensus
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procedure for disagreements, and a search in ≥2 electronic
sources).
Because the AMSTAR 2 tool does not have established
categories of quality, the included systematic reviews and
meta-analyses were grouped according to the number of
criteria met as follows: excellent, 15–16; very good, 12–
14; good, 9–11; acceptable, 6–8; and deficient, 3–5; 23.5%
of studies scored as acceptable, 17.6% as good, 52.9% as
very good, and 5.9% as excellent in terms of risk of bias
(54) (Supplemental Table 2). When individual domains were
considered, no studies reported a list of excluded studies,
and 88.2% of the studies did not report the included studies’
funding information.
The certainty of evidence for the considered meta-
analyses was assessed by using Grading of Recommendations
Assessment, Development and Evaluation (GRADE) (Sup-
plemental Tables 3–5).
Updated meta-analysis of RCTs and biomarkers of car-
diometabolic risk.
We performed an updated meta-analysis for the RCTs
published from 2013 to 2018. Two authors (JF and AG)
independently assessed the risk of bias of selected RCTs
following the Cochrane Collaboration’s methodology (55).
In case of discrepancies, a third reviewer was involved in
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TABLE 2 Characteristics of the meta-analyses of RCTs evaluating the effects of dairy product consumption on blood lipids1

Intervention
Author RCTs, n Participants, n Age,2 y Exposure observed time, wk Blood lipids Changes,3 mmol/L Heterogeneity4

Supplement
Agerholm-Larsen et 5 70 39.4 ± 2.1 Fermented dairy products 4–8 Total-C − 0.23 (−0.41, −0.05) 7.22 (df = 4, P = 0.88)
al. (24) LDL-C − 0.25 (−0.48, −0.01) 8.88 (df = 4, P = 0.94)
Sun and Buys (25) 15 788 >18 Fermented milk or yogurt >8 Total-C − 0.27 (−0.38, −0.16) 35.5%
LDL-C − 0.23 (−0.33, −0.13) 56.6%
Benatar et al. (26) 9 702 51 ± 16 Total dairy products 26 LDL-C 0.05 (−2.89, 6.60) 64.0%
Whole-fat dairy vs. − 0.005 (−2.10, 1.71) 0.0%
low-fat
de Goede et al. (27) 5 5–49 22–56 Cheese vs. butter 2–8 Total-C − 0.28 (−0.36, −0.19) 0.0%
LDL-C − 0.22 (−0.29, −0.14) 0.0%
Shimizu et al. (28) 11 13–152 All ages Fermented milk products 4–8 Total-C − 0.17 (−0.27, −0.07) 59%
and probiotics LDL-C − 0.22 (−0.30, −0.13) 41%
1
Servings per day were converted into grams per day. LDL-C, LDL cholesterol; RCT, randomized controlled trial; total-C, total cholesterol.
2
Values are means ± SDs or ranges.
3
Values are changes (95% CIs).
4
Values are Q values when the heterogeneity of effect size was tested with Q statistics based on chi-square distribution (P < 0.05 was considered statistically significant), or I2 (%) when the test for heterogeneity was assessed via the I2 statistic,
which expresses the percentage of variation attributable to between-study heterogeneity.

TABLE 3 Characteristics of the meta-analyses of RCTs evaluating the effects of dairy consumption on blood pressure1

Author RCTs, n Participants, n Age,2 y Intervention time Exposure observed Blood pressure Changes3 (mm Hg) Heterogeneity4
Ding et al. (29) 8 753 20–71 1–12 mo Total dairy products DBP −0.21 (−0.98, 0.57) 0.0%
Hidayat et al. (30) 7 412 23.4–61.1 1–24 mo Total dairy products SBP −3.33 (−5.62, −1.03) 0.0%
DBP −1.08 (−3.38, −0.22) 0.0%
Benatar et al. (26) 20 1677 51 ± 16 26 wk Total dairy products SBP −0.41 (−1.60, 0.81) 0.0%
DBP −0.45 (−1.70, 0.80) 40.0%
Cicero et al. (31) 14 1306 40–58 4–21 wk Total dairy products SBP −1.28 (−2.09, −0.48) P = 0.13
DBP −0.59 (−1.18, −0.01)
Dong et al. (32) 14 702 39–75 4–24 wk Probiotic fermented milk SBP −3.10 (−4.64, −1.56) 24.1%
DBP −1.09 (−2.11, −0.06) 29.0%
Turpeinen et al. (33) 19 1500 35–70 4–21 wk Total dairy products SBP −4.00 (−5.90, −2.10) 75.0%
DBP −1.90 (−3.10, −0.80) 70.0%
Usinger et al. (34) 15 1232 ≥18 ≥4 wk Fermented milk SBP −2.45 (−4.30, −0.60) 71.0%
DBP −0.67 (−1.48, 0.14) 39.0%
Xu et al. (35) 12 623 43–75 4–21 wk Milk-derived tripeptides SBP −4.80 (−6.00, −3.70) 16.2, P > 0.1
IPP-VPP DBP −2.20 (−3.10, −1.30) 11.5, P > 0.25
1
DBP, diastolic blood pressure; IPP-VPP, isoleucine, proline, proline-valine, proline, proline; RCT, randomized controlled trial; SBP, systolic blood pressure.
2
Values are means ± SDs or ranges.
3
Values are changes (95% CIs).
4
Values are Q values when the heterogeneity of effect size was tested with Q statistics based on chi-square distribution (P < 0.05 was considered statistically significant), or I2 (%) when the test for heterogeneity was assessed via the I2 statistic,
which expresses the percentage of variation attributable to between-study heterogeneity.

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 TABLE 4 Characteristics of the randomized controlled trials included and published from 2013 to 2018 for blood lipids and blood pressure biomarkers1

Type of study
Authors
Drouin-Chartier et al.
(56)
Drouin-Chartier et al.
(57)
Fathi et al. (58)
Machin et al. (59)
Tanaka et al. (60)
Maki et al. (61)
Rideout et al. (62)
Conway et al. (63)
Conway et al. (64)
Benatar et al. (65)
Soerensen et al. (66)
Raziani et al. (67)
1
CO, crossover; DBP, diastolic blood pressure; LDL-C, LDL cholesterol; ND, not determined; P, prospective; SBP, systolic blood pressure; total-C, total cholesterol.
2
Values are means ± SDs or ranges.
3
Values are changes (95% CIs).
Sample Subjects’ age (y), BMI (kg/m2 ), Period of Changes in blood pressure Changes in plasma lipids
(P or CO) size (n) and other characteristics2 Exposure Dosage intervention (SBP and DBP) (mm Hg)3 (total-C and LDL-C) (mmol/L)3
CO 76 Age: 53.3 ± 12.2; BMI: 28.2 ± 3.7 Dairy products 3.4 servings dairy 4 wk SBP = −1.0 (−3.86, 1.86) ND
products/d DBP = 0.00 (−2.71, 2.71)
CO 27 Age: 57 ± 5.0; BMI: 31.9 ± 3.5 Milk 3.2 servings 2% fat 6 wk ND Total-C = 0.07 (−0.37, 0.51)
milk/d LDL-C = −0.01 (−0.41, 0.39)
P 75 Age: 25–45; BMI: 25–34.9 Dairy products Milk 8 wk ND Total-C = −0.26 (−0.31, −0.21)
LDL-C = −0.24 (−0.28, −0.20)
Kefir Total-C = −0.41 (−0.46, −0.36)
LDL-C = −0.40 (−0.44, −0.36)
CO 49 Age: 53 ± 2; BMI: 30.5; elevated Dairy products High-dairy (+4 4 wk ND Total-C = 0.10 (0.02, 0.18)
blood pressure servings LDL-C = 0.03 (−0.01, 0.07)
conventional
nonfat dairy
products/d)
P 200 Age: 20–60; BMI: 25 Dairy products 400 g dairy 24 wk SBP = 2.20 (−1.68, 6.08) Total-C = 0.20 (−0.02, 0.42)
products/d DBP = 2.00 (−1.04, 5.04) LDL-C = 0.23 (0.04, 0.42)
CO 62 Age: 54.5; BMI: 29.2 Dairy products 1 serving low-fat 5 wk ND Total-C = 0.03 (0.01, 0.05)
dairy/d LDL-C = 0.02 (0.01, 0.03)
CO 23 Age: 18–75; BMI: 18.5–35.0 Dairy products Low dairy (<2 1y SBP = −1.20 (−11.07, 8.67) Total-C = −0.33 (−0.78, 0.12)
servings dairy DBP = 0.70 (−8.02, 9.42) LDL-C = −0.19 (−0.59, 0.21)
products/d)
High dairy (4 servings SBP = −3.80 (−13.24, 5.64) Total-C = −0.13 (−0.54, 0.28)
dairy products/d) DBP = −1.20 (−8.04, 5.64) LDL-C = −0.09 (−0.49, 0.31)
CO 34 Age: 18 and 65; BMI: ≤35 Buttermilk 45 g buttermilk/d 4 wk ND Total-C = −0.18 (−0.60, 0.24)
LDL-C = −0.12 (−0.44, 0.20)
CO 34 Age: 18 and 65; BMI: ≤35 Buttermilk 45 g buttermilk/d 4 wk SBP = −2.60 (−7.88, 2.68) ND
DBP = −1.20 (−5.22, 2.82)
P 180 Age: 46.7 ± 1.7; BMI: 24.5 ± 0.3 Dairy products Low dairy intake 4 wk SBP = −1.20 (−4.91, 2.51) LDL-C = −0.11 (−0.41, 0.19)
Medium dairy intake DBP = −1.90 (−4.78, 0.98)
High dairy intake SBP = 0.90 (−3.09, 4.89) LDL-C = −0.09 (−0.40, 0.22)
DBP = −2.50 (−5.49, 0.49)
SBP = −0.10 (−3.69, 3.89) LDL-C = 0.07 (−0.22, 0.36)
DBP = −0.50 (−3.39, 2.39)
CO 15 Age: 18–50; BMI: 20–28 Milk Semi-skimmed milk 3 × 2 wk SBP = −0.80 (−6.84, 5.24) Total-C = −0.29 (−1.03, 0.45)
(1700 mg Ca/d)]. DBP = −1.40 (−6.52, 3.72) LDL-C = −0.33 (−1.02, 0.36)
Cheese Semihard cow SBP = −2.00 (−6.81, 2.81) Total-C = −0.28 (−1.00, 0.44)
cheese (1700 mg DBP = −1.20 (−6.05, 3.65) LDL-C = −0.24 (−0.91, 0.43)
Ca/d)].
P 139 Age: 18–70; BMI: 18.5–37.5 Cheese Regular-fat cheese 12 wk SBP = 2.00 (−4.16, 8.16) Total-C = 0.16 (0.10, 0.22)
Reduced-fat cheese DBP = −0.30 (−3.94, 3.34) LDL-C = 0.08 (0.03, 0.13)
SBP = −1.20 (−7.29, 4.89) Total-C = 0.04 (−0.02, 0.10)
DBP = −1.90 (−5.56, 1.76) LDL-C = 0.02 (−0.03, 0.07)

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the evaluation (VM-V). The Cochrane tool includes differ-
ent domains related to random assignment and allocation
concealment (selection bias), blinding (performance and
measurement bias), loss to follow-up and adherence to
the intention-to-treat principle (attrition bias), and selective
outcome publication (reporting bias). In addition, other
potential sources of bias, such as private or public funding,
were included. The risk of bias was tabulated for each study
and was classified as low, high, or unclear, as described in
Chapter 8 of the Cochrane Handbook for Systematic Reviews
of Interventions (55).
The majority of RCTs selected for the update lacked
specific reporting of the allocation concealment and because
of the nature of the interventions it was not possible to follow
a double-blind design. The detection bias is another concern
owing to the insufficient details provided by the authors in
relation to the blinding of the people who assessed the clinical
outcomes. However, we did not detect a potential bias in the
reporting of outcome data (Supplemental Figures 3 and 4).
Display of the results
Observational cohort studies and major cardiovascular
outcomes.
Forest plots were used to display the pooled risk ratio
estimates for the association between dairy products and
cardiovascular outcomes in the included studies. Forest plots
were performed considering the relation between each main
cardiovascular outcome (CVD, CHD, and stroke) and 1)
dairy product exposure (high compared with low intake or
dose-response) and 2) the dairy product subgroup (total
dairy products, milk, cheese, yogurt, and butter). To be
included in the forest plot, the pooled risk ratio reported by
meta-analyses should include ≥4 studies. Forest plot graphs
were created using Stata SE software, version 15 (StataCorp).
For studies that reported dairy product consumption as
servings per day, we considered a single serving of milk as
244 g, a serving of cheese as 35 g, and 1 serving of total dairy,
high-fat dairy, and low-fat dairy as 200 g, similar to previous
meta-analyses (13).
RCTs and biomarkers of cardiometabolic risk.
Forest plots were also used to display the pooled risk
ratio estimates for the associations between dairy products
and biomarkers of cardiometabolic risk in the included
meta-analyses. Forest plots were performed considering the
relation with each main risk outcome, e.g., SBP and DBP, total
cholesterol, and LDL cholesterol.
We performed the corresponding meta-analyses for these
outcomes with RCTs published from January 2013 to 2018
to update the potential effects of milk and dairy products
on some biomarkers of cardiometabolic risk, namely blood
pressure and blood lipids. The main outcome variables for
the meta-analyses were the absolute changes in SBP and
DBP (mm Hg) and the total cholesterol and LDL-cholesterol
concentrations (mmol/L) between the intervention and
control groups. The variance measures for the absolute
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changes in the outcomes were reported as means and 95%
CIs.
Pooled effect sizes were calculated for the absolute changes
in the outcomes after the dairy product interventions
using a random-effects model, which takes into account
within- and between-study variation. The estimated results
were displayed as forest plots. Between-study heterogeneity
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was quantified using the I2 statistic. Because the presence
of heterogeneity may affect the statistical validity of the
summary estimate of effect, the Q statistic was used to test
the null hypothesis of statistical validity; P values <0.05 were
considered significant.
Sensitivity analyses were conducted to assess whether any
single study exerted undue influence on the overall results.
This was conducted by excluding 1 study at a time from
the analyses and recalculating the effect size each time.
Publication bias was visually assessed using a funnel plot (68).
Statistical analysis was conducted using the R free soft-
ware environment for statistical computing and graphics,
version 3.4.4 (R Foundation for Statistical Computing).
The “metafor” meta-analysis package for R was used for
calculations and data visualizations.
Results
Dairy product consumption and cardiovascular
outcomes
Table 1 shows the characteristics of the meta-analyses
included in the present study and the RRs for dairy intake
and incident CVD, CHD, and stroke (high compared with
low consumption, regular- compared with low-fat content,
and dose–response intake).
Total dairy products.
The association between high compared with low total
dairy product consumption and CVD (total incidence
and mortality), CHD, and stroke was analyzed in several
meta-analyses. Collectively, the intake of dairy products
was not associated with CVD. Moreover, 2 meta-analyses
(12, 15) reported a significant negative association (RR:
0.88; 95% CI: 0.81, 0.96 and RR: 0.90; 95% CI: 0.81,
0.99, respectively) (Figure 2). Guo et al. (14) did not
find evidence of a significant association between a 200
g/d increment of total or high- or low-fat dairy product
consumption (dose-response) and CVD risk (Figure 3).
The risk of CHD (total, incidence, or mortality) was
studied in 5 meta-analyses (Figure 4). Globally, total dairy
product intake was neutral for CHD risk and the same results
were found for consumption of high-fat dairy products. A
significantly lower risk was found for low-fat dairy products
(RR: 0.90; 95% CI: 0.82, 0.98) (13). Other authors (43, 45)
also found significantly lower risk of IHD (RR: 0.84; 95%
CI: 0.76, 0.93 and RR: 0.92; 95% CI: 0.80, 0.99, respectively).
MI was studied in 1 meta-analysis (45) and the results also
showed a significantly reduced risk with high consumption
of total dairy products (RR: 0.83; 95% CI: 0.66, 0.99) (Figure
4). On the other hand, in 1 meta-analysis (42) the association

FIGURE 2 Forest plot for meta-analyses evaluating the influence of high compared with low dairy product consumption on CVD. The
effect size and 95% CI for fully adjusted random effects are depicted for each meta-analysis. CVD, cardiovascular disease.
of dairy product intake with the incidence of heart failure
risk was analyzed and no significant association was found
(Figure 4).
The dose-response for CHD and total dairy products was
considered in 4 meta-analyses (Figure 5). Three found no
significant differences with an intake increase of 200 g/d
(14, 42, 52). Alexander et al. (13) analyzed the consumption
of <300 g/d, 300–600 g/d, and >600 g/d and reported
significantly lower risk of CHD with increments of 300 g/d
and 600 g/d (RR: 0.88; 95% CI: 0.80, 0.96 and RR: 0.90; 95%
CI: 0.79, 0.94, respectively). An increment of consumption of
200 g/d of low- or high-fat dairy products was not associated
with CHD (43, 52).
Seven meta-analyses analyzed the risk of stroke (total
incidence or mortality) with the consumption of total dairy
products (Figure 6). Six (12, 13, 15, 45, 46, 48) reported an
inverse statistically significant association (RR: 0.87; 95% CI:
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0.77, 0.99; RR: 0.91; 95% CI: 0.83, 0.99; RR: 0.88; 95% CI:
0.82, 0.95; RR: 0.79; 95% CI: 0.75, 0.92; RR: 0.93; 95% CI:
0.88, 0.98; and RR: 0.88; 95% CI: 0.82, 0.94, respectively). The
same results were found for stroke mortality in 2 studies (16,
48) (RR: 0.80; 95% CI: 0.76, 0.84 and RR: 0.80; 95% CI: 0.76,
0.83, respectively).
The association between consumption of regular-fat and
low-fat total dairy products and stroke was followed in 5
meta-analyses; 2 (13, 42) found significantly lower risk with
high-fat products (RR: 0.91; 95% CI: 0.84, 0.99 and RR: 0.93;
95% CI: 0.87, 0.99, respectively). A high consumption of
low-fat dairy products was also reported to have an inverse
association with the risk of stroke (12, 46, 48): RR: 0.93; 95%
CI: 0.88, 0.99; RR: 0.91; 95% CI: 0.85, 0.97; and RR: 0.94;
95% CI: 0.90, 0.98 (Figure 6). Moreover, similar results were
found for dose-response of 300 g/d or 450 g/d of total dairy
products (13) (RR: 0.92; 95% CI: 0.89, 0.96 and RR: 0.91;
Dairy products and cardiovascular disease S175

FIGURE 3 Forest plot for meta-analyses evaluating the influence of dose-response of dairy product consumption on CVD. The effect size
and 95% CI for fully adjusted random effects are depicted for each meta-analysis. CVD, cardiovascular disease.
95% CI: 0.88, 0.95, respectively) or for each increment of 200
g/d of high- or low-fat dairy products (47) (RR: 0.96; 95%
CI: 0.93, 0.99 and RR: 0.97; 95% CI: 0.95, 0.99, respectively)
(Figure 7).
The association of ischemic stroke risk with total dairy
consumption was considered in 4 meta-analyses (Figure 6).
Elwood et al. (43) found a statistically significant inverse
association (RR: 0.79; 95% CI: 0.68, 0.91). However, in
the rest of the studies (13, 42, 48), no association was
observed. Hemorrhagic stroke was reported in 3 meta-
analyses (Figure 6); only 1 (43) found a statistically significant
inverse association (RR: 0.75; 95% CI: 0.60, 0.94). With an
increment of consumption of 200 g/d, no association with
ischemic or hemorrhagic stroke or stroke mortality was
found (47) (Figure 7).
Milk.
The association between high or low milk consumption
and CVD incidence (Figure 2) was examined in 2 meta-
analyses (13, 44); 1 of them found a significant protective
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effect (RR: 0.84; 95% CI: 0.78, 0.90) (44). Milk consumption
was not significantly associated with increased CHD risk
in 2 meta-analyses (13, 46) or with IHD (44) (Figure 5).
Five studies analyzed fatal and nonfatal stroke events with
total milk consumption (13, 44, 46, 48, 52). A significant
inverse association between stroke and milk consumption
(RR: 0.83; 95% CI: 0.77, 0.90) was found by Elwood et
al. (44), whereas no association was reported for the rest
of the meta-analyses. No association between total milk
intake and ischemic or hemorrhagic stroke was found (13)
(Figure 6).
Two studies performed a dose–response analysis for milk
consumption and CVD (Figure 3), with increments of intake
of 200 g/d (52) and 244 g/d (14), but only the first reported
a significant inverse effect (RR: 0.94; 95% CI: 0.89, 0.96).
However, no association was found between an increase in
milk intake and CHD incidence (Figure 5) in any of the
4 research groups examining this outcome (13, 14, 50, 52).
Three studies (13, 47, 50) examined the association between
total stroke events and the increment of milk intake (Figure
7), but only 1 found a significant inverse association (RR:
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FIGURE 4 Forest plot for meta-analyses evaluating the influence of high compared with low dairy product consumption on CHD. The
effect size and 95% CI for fully adjusted random effects are depicted for each meta-analysis. CHD, coronary heart disease.

Dairy products and cardiovascular disease S177

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FIGURE 5 Forest plot for meta-analyses evaluating the influence of dose-response of dairy product consumption on CHD. The effect size
and 95% CI for fully adjusted random effects are depicted for each meta-analysis. CHD, coronary heart disease.

0.93; 95% CI: 0.88, 0.98) in the case of an increment of Cheese.

200 g/d (47). This study also reported a significantly lower
risk of stroke mortality with milk consumption (RR: 0.88;
95% CI: 0.81, 0.96), although no association with ischemic
or hemorrhagic stroke was observed. Regarding milk fat
content, only 1 study observed a significant increase of the
total stroke risk (RR: 1.04; 95% CI: 1.02, 1.06) with an
intake increment of 200 g/d of high-fat milk, whereas no
association was reported for the same increment of low-fat
milk consumption (47).
In the last few years, 3 studies investigated the association
between high compared with low cheese consumption and
CVD risk (Figure 2). One reported an inverse association
(16) (RR: 0.90; 95% CI: 0.82, 0.99); in the other 2 meta-
analyses no associations were found (13, 43). High- and low-
fat cheese intake was studied and no association with CVD
risk was observed (16) (Figure 2). Dose-response with 10
g/d (15) or 50 g/d (16) consumption was also reported to be
neutral regarding risk of CVD (Figure 3).

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FIGURE 6 Forest plot for meta-analyses evaluating the influence of high compared with low dairy product consumption on stroke. The
effect size and 95% CI for fully adjusted random effects are depicted for each meta-analysis.

Dairy products and cardiovascular disease S179

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FIGURE 7 Forest plot for meta-analyses evaluating the influence of dose-response of dairy product consumption on stroke. The effect
size and 95% CI for fully adjusted random effects are depicted for each meta-analysis.

For CHD (Figure 4), 2 meta-analyses (13, 16) found a
significantly lower risk (RR: 0.82; 95% CI: 0.72, 0.93 and RR:
0.86; 95% CI: 0.77, 0.96, respectively) and 2 others found
no statistical significance (13, 52). The intake of high- or
low-fat cheese was not significantly associated with CHD
(16). The dose-response for cheese intake of 50 g/d (13,
16) and 75 g/d (13) was associated with significantly lower
CHD risk (RR: 0.86; 95% CI: 0.75, 0.97; RR: 0.90; 95% CI:
0.84, 0.95; and RR: 0.92; 95% CI: 0.87, 0.97, respectively)
(Figure 5).
Cheese intake was inversely associated with stroke in 4
meta-analyses (12, 13, 16, 46) (Figure 6) (RR: 0.91; 95% CI:
0.84, 0.98; RR: 0.87; 95% CI: 0.77, 0.97; RR: 0.90; 95% CI:
0.84, 0.97; and RR: 0.93; 95% CI: 0.88, 0.99, respectively).
In another meta-analysis (48), cheese consumption was not
significantly associated with stroke.

S180 Supplement
 Moreover, a dose–response study (13) reported a sig-
nificantly lower risk of stroke when the cheese intake was
increased by 50 g/d (RR: 0.86; 95% CI: 0.77, 0.99) or 75 g/d
(RR: 0.92; 95% CI: 0.87, 0.97) (Figure 7).
Yogurt and fermented products.
The relation between yogurt intake and CVD (Figure
2) was examined in 2 meta-analyses (13, 53), with no
significant association reported. Similarly, no effect of yogurt
consumption on CHD risk was found (12, 13, 53) (Figure 4).
For risk of stroke, no significant effect was reported (12, 53)
(Figure 6). Regarding yogurt intake, increments of 50 g/d (14)
and 100 g/d (47) were not related to fatal and nonfatal events
in CHD (Figure 5) or stroke (Figure 7).
On the other hand, consumption of fermented milk
significantly reduced the risk of stroke (48) (RR: 0.80; 95%
CI: 0.71, 0.89) (Figure 6). Considering the dose-response,
an increment of 200 g/d in the intake of fermented dairy
products significantly reduced the risk of CVD (14) (RR:
0.98; 95% CI: 0.97, 0.99) (Figure 3) and it was also inversely
associated with stroke mortality risk (47) (RR: 0.80; 95% CI:
0.67, 0.95) (Figure 7). Another study (14) did not find an
association between CHD risk and an intake increment of 20
g/d of fermented dairy products (Figure 5). A neutral effect
on stroke was also observed (47) when the consumption of
fermented dairy products was increased by 200 g/d (Figure
7).
Butter and cream.
Five meta-analyses analyzed the relation between butter
consumption and different vascular diseases (Figures 2
and 6), and no significant effects were reported for CVD
(24), CHD (12, 46), and stroke (12, 47, 52, 53). Likewise,
no significant effect for stroke risk was found for cream
consumption, as reported in 2 studies (46, 48).
With regard to dose–response analyses (Figures 3and 7),
no evidence of a significant association between an increment
in butter consumption of 10 g/d and stroke was found (47).
Another study also reported no association with CVD or
CHD after increasing butter intake by 14 g/d (51).
Dairy product consumption and biomarkers of
cardiometabolic risk
The characteristics of the meta-analyses of RCTs evaluating
the effects of dairy product consumption on blood lipid
biomarkers (total cholesterol and LDL cholesterol) are shown
in Table 2 and Figure 8. Fermented dairy product intake
was inversely associated with total cholesterol and LDL
cholesterol in 4 meta-analyses (24, 25, 27, 28); however, 1
meta-analysis did not find significant differences for LDL
cholesterol when comparing the consumption of whole-fat
dairy with low-fat dairy products (26). The effect of dairy
product consumption on blood pressure biomarkers was
evaluated in 8 studies (Table 3, Figure 9) and 6 of them (30–
35) found a significant reduction of SBP, whereas 5 studies
(30–33, 35) also reported a significant DBP decrease.
In addition, we identified 30 RCTs published between
2013 and 2018 quantifying the association between dairy
product consumption and blood pressure, as well as plasma
lipids related to risk of CVD, particularly total cholesterol
and LDL cholesterol, but only 12 RCTs were selected for
meeting the inclusion criteria (56–67). Table 4 presents the
descriptive information of the RCTs evaluating the effects
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of milk and dairy product consumption. Figures 10 and 11
depict the results for the meta-analyses describing the effects
of dairy product consumption on the blood lipid biomarkers
total cholesterol and LDL cholesterol, and on SBP and DBP.
No significant changes were found for both total cholesterol
(−0.06 mmol/L; 95% CI: −0.19, 0.07 mmol/L) and LDL
cholesterol (−0.06 mmol/L; 95% CI: −0.16, 0.03 mmol/L)
related to the consumption of dairy products (overall effect
Z = −0.96, P = 0.34, and Z = −1.26, P = 0.21, respectively).
Figure 10A, B shows these changes and combined estimates
along with 95% CIs. Similarly, dairy product consumption
did not result in significant changes for SBP and DBP (mm
Hg) (SBP = −0.41; 95% CI: −1.73, 0.91; P = 0.93 and
DBP = −0.77; 95% CI: −1.81, 0.27; P = 0.87) (Figure 11A,
B).
The overall average between-trial heterogeneity (I2 ) was
high for total cholesterol: 97.0% (95% CI: 91.76%, 98.78%)
(Q = 411.55, df = 12, P < 0.001), and for LDL cholesterol:
96.9% (95% CI: 91.36%, 98.40%) (Q = 572.86, df = 15,
P < 0.001). Nevertheless, for blood pressure biomarkers, the
heterogeneity (I2 ) was low for SBP: 0.0% (95% CI: 0.00%,
20.28%) (Q = 4.83, df = 11, P = 0.93), as well as for DBP: 0.0%
(95% CI: 0.00%, 30.14%) (Q = 6.11, df = 11, P = 0.87).
The sensitivity study of bias for the selected RCTs is
depicted in funnel plots (Supplemental Figures 5–8).
Discussion
Recently, a systematic review and meta-analysis of prospec-
tive population-based studies including people with CVD
and other noncommunicable chronic diseases, namely hy-
pertension, metabolic syndrome, and type 2 diabetes, pro-
vided evidence supporting a negative relation between intake
of total dairy, low-fat dairy, cheese, and fermented dairy
and the risk of stroke (17), although conclusions were not
uniform.
This overview of systematic reviews and meta-analyses
provides a synthesis of the state of knowledge related to
the association between dairy product consumption and
CVD. The main findings of the present study stated that the
consumption of total dairy products, with either regular- or
low-fat content or with different dose-responses, revealed no
association or lower risk of different outcomes such as total
incidence and mortality for CVD, CHD, and ischemic and
hemorrhagic stroke.
We also have reviewed the published meta-analyses of
RCTs that investigated the potential effects of the consump-
tion of dairy products on selected biomarkers of CVD risk,
i.e., total cholesterol, LDL cholesterol, and blood pressure,
and made a new updated meta-analysis including the RCTs
published from 2013 to 2018. The main findings of the
Dairy products and cardiovascular disease S181

FIGURE 8 Forest plot for meta-analyses of randomized controlled trials evaluating the influence of consumption of dairy products on
blood lipids: total-C (A) and LDL-C (B). The ES and 95% CI for fully adjusted random effects are depicted for each meta-analysis. ES, effect
size; LDL-C, LDL cholesterol; total-C, total cholesterol.
present study add further evidence to the hypothesis that
dairy product consumption does not adversely affect blood
lipids and blood pressure. Besides, some types of dairy
products, such as fermented milks (i.e., yogurt, kefir, and
cheese), clearly decrease those CVD risk biomarkers, which
is in accordance with previous reports by other authors (8,
17, 18).
The information provided in this study updates the
scientific evidence published up to April 2018 and includes
a high number of recent meta-analyses. In comparison with
other similar studies published in recent years, this work
examines, critically and in detail, all the data and potential
mechanisms described in other reviews that are aimed at
elucidating the effects of the consumption of milk, fermented
dairy products such as yogurt and cheeses, and cream and
butter at different doses, and the possible detrimental effect
of their fat content.
Current dietary recommendations recognize the contri-
bution of milk and dairy products to a healthy diet because
their consumption contributes to meeting the needs for
many high-quality nutrients. Nevertheless, regular milk and
dairy products containing milk fat are major food sources
of SFAs, and this has been linked to an increased risk of
CVD. However, the results obtained in this systematic review
showed inverse or no association with CVD, CHD, or stroke.
The effects of milk or dairy product consumption on
health depend on the interaction of all their nutrients,
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going beyond the mere sum of their individual effects.
Thus, considering only 1 macronutrient, such as SFA, in
a complex food such as milk may give rise to mistaken
interpretations because not all SFAs have the same effect on
plasma cholesterol [e.g., stearic acid (C18:0) is desaturated
at the 9-position mainly in the liver to give oleic acid] (69,
70). Moreover, it has been reported that although dairy
SFAs may have a negative effect on some cardiovascular
indicators, such as an increase in total cholesterol and LDL
cholesterol, they may give rise to increases in concentrations
of HDL cholesterol that reverse cholesterol transport path-
ways, inhibit LDL-cholesterol oxidation, and thus prevent
subsequent inflammatory processes (71). In addition, the
dairy SFA increase in LDL cholesterol results in large,
buoyant, and fluffy LDL particles, which are more resistant
to oxidation and therefore less atherogenic than small, dense
LDL particles (4, 5).
Moreover, individual SFAs possess specific properties
associated with important biological functions, such as
butyric acid, uniquely present in dairy products, which,
in addition to being a compound with high biological
activity, contributes significantly to the total SCFAs. The
latter also contribute to the potential beneficial health effects
of medium-chain TGs that have been shown to exert
antibacterial activity (72), have a low tendency to be stored in
adipose tissue, improve body composition without adversely
affecting cardiometabolic risk factors, and not have an effect
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FIGURE 9 Forest plot for meta-analyses of randomized controlled trials evaluating the influence of consumption of dairy products on
SBP (A) and DBP (B). The effect size and 95% CI for fully adjusted random effects are depicted for each meta-analysis. DBP, diastolic blood
pressure; IPP-VPP, isoleucine, proline, proline-valine, proline, proline; SBP, systolic blood pressure.

on the increase of cholesterol concentrations in blood (73–
76).
In addition, SCFAs can interact with G-protein-coupled-
receptors GPR41 and GPR43, leading to an increase in the
intestinal secretion of glucagon-like peptide 1 and other
incretins, which in turn can enhance satiety. Furthermore,
SCFAs seem to activate AMP-activated protein kinase in
muscles, increasing insulin sensitivity and fatty acid oxida-
tion and decreasing lipid accumulation (77).
Milk fat also has appreciable amounts of SFAs with odd-
numbered chains of carbon atoms (C15 and C17), which are
used in clinical studies as markers of human consumption
of regular dairy products. Plasma concentrations of those
fatty acids were associated with a lower incidence of diabetes
mellitus, and nonassociation or even a protective effect
on CVD has been documented (78–80). Other SFAs, such
as those that are methyl-branched, are also present, with
interest for intestinal health and for which anti-inflammatory
properties have been documented (80). Therefore, both
groups of SFAs would not seem to have a negative impact on
CVD.
It is also important to highlight the presence of other
bioactive lipid components, such as conjugated linoleic acid
and sphingolipids, for which benefits have been described in
diseases related to the immune system and nervous system
development and for potential cardioprotective effects (3,
81).
Despite the current evidence suggesting null or weak
inverse association between consumption of dairy products
and risk of CVD, some investigators, based on substitution
analyses, continue claiming that replacing dairy fat with
polyunsaturated fat, especially from plant-based foods, may
confer health benefits (82, 83). Nonetheless, it is important
to state that milk and dairy products are a combination of
nutrients and bioactive substances, such as peptides, fatty
acids, minerals, and vitamins, that interact with each other
in the dairy matrix, and therefore, the overall effect on health
after their consumption is not what is expected based on their

Dairy products and cardiovascular disease S183

 A
Conway et al. (2013) (63) − Buttermilk 5.18% −0.18 [−0.60, 0.24]
Maki et al. (2013) (61) −Dairy 11.27% 0.03 [ 0.01, 0.05]
Rideout et al. (2013) (62) − Low Dairy 4.80% −0.33 [−0.78, 0.12]
Rideout et al. (2013) (62) − High Dairy 5.23% −0.13 [−0.54, 0.28]
Machin et al. (2014) (59) − High dairy 10.83% 0.10 [ 0.02, 0.18]
Soerensen et al. (2014) (66) − Milk 2.42% −0.29 [−1.03, 0.45]
Soerensen et al. (2014) (66) − Cheese 2.50% −0.28 [−1.00, 0.44]

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Tanaka et al. (2014) (60) − Dairy 8.55% 0.20 [−0.02, 0.42]
Drouin−Chartier et al. (2015) (57) − Milk 4.94% 0.07 [−0.37, 0.51]
Raziani et al. (2016) (67) − Regular Fat Cheese 11.06% 0.16 [ 0.10, 0.22]
Raziani et al. (2016) (67) − Reduced Fat Cheese 11.05% 0.04 [−0.02, 0.10]
Fathi et al. (2017) (58) − Milk 11.08% −0.26 [−0.31, −0.21]
Fathi et al. (2017) (58) − Kefir 11.10% −0.41 [−0.46, −0.36]
RE Model 100.00% −0.06 [−0.19, 0.07]

−1.5 −1 −0.5 0 0.5 1

Mean Difference

B
Conway et al. (2013) (63) − Buttermilk 4.79% −0.12 [−0.44, 0.20]
Maki et al. (2013) (61) −Dairy 9.78% 0.02 [ 0.01, 0.03]
Rideout et al. (2013) (62) − Low Dairy 3.72% −0.19 [−0.59, 0.21]
Rideout et al. (2013) (62) − High Dairy 3.72% −0.09 [−0.49, 0.31]
Benatar et al. (2014) (65) − Low Dairy 5.05% −0.11 [−0.41, 0.19]
Benatar et al. (2014) (65) − Medium Dairy 5.03% −0.09 [−0.40, 0.22]
Benatar et al. (2014) (65) −High Dairy 5.27% 0.07 [−0.22, 0.36]
Machin et al. (2014) (59) − High dairy 9.65% 0.03 [−0.01, 0.07]
Soerensen et al. (2014) (66) − Milk 1.67% −0.33 [−1.02, 0.36]
Soerensen et al. (2014) (66) − Cheese 1.78% −0.24 [−0.91, 0.43]
Tanaka et al. (2014) (60) − Dairy 7.26% 0.23 [ 0.04, 0.42]
Drouin−Chartier et al. (2015) (57) − Milk 3.76% −0.01 [−0.41, 0.39]
Raziani et al. (2016) (67) − Regular Fat Cheese 9.60% 0.08 [ 0.03, 0.13]
Raziani et al. (2016) (67) − Reduced Fat Cheese 9.57% 0.02 [−0.03, 0.07]
Fathi et al. (2017) (58) − Milk 9.67% −0.24 [−0.28, −0.20]
Fathi et al. (2017) (58) − Kefir 9.66% −0.40 [−0.44, −0.36]
RE Model 100.00% −0.06 [−0.16, 0.03]

−1.5 −1 −0.5 0 0.5

Mean Difference

FIGURE 10 Forest plot for the updated meta-analyses of randomized controlled trials included from 2013 to 2018 evaluating the
influence of consumption of dairy products on total-C (A) and LDL cholesterol (B) plasma concentrations. The effect size and 95% CI for
fully adjusted random effects are depicted for each RCT. Pooled effect estimate is represented by the black diamond. (A) Total-C: overall
effect Z = −0.96, P = 0.34; heterogeneity I2 = 97.0% (91.76%, 98.78%) (Q = 411.55, df = 12, P < 0.001). (B) LDL cholesterol: overall effect
Z = −1.26, P = 0.21; heterogeneity I2 = 96.9% (91.36%, 98.40%) (Q = 572.86, df = 15, P < 0.001). RE, random effects; Total-C, total
cholesterol.

nutritional content. Thus, for regular milk with its whole fat,
or dairy products such as cheese with its fat and salt content,
the majority of studies report that they do not increase the
risk of CVD and may, in fact, be beneficial (10, 70).
In addition, possible mechanisms are suggested in ran-
domized studies that would explain the neutral or inverse
association of consumption of regular dairy products with
CVD outcomes. RCTs have documented that cheese con-
sumption was negatively associated with plasma TG and
positively associated with HDL cholesterol (84, 85). The
possible mechanism is related to the decrease in plasma TG
synthesis owing to the presence of inhibitors of fatty acid
desaturases in cheese (86).
On the other hand, the major milk proteins contain all the
essential amino acids required to meet our nutritional needs,
and they are defined as high-quality proteins and exhibit
high availability and digestibility. Moreover, gastrointestinal
digestion of milk proteins generates bioactive peptides that
are reported to have numerous beneficial effects on health
and are associated with a lower risk of hypertension (87, 88).
Calcium is the milk mineral of greatest interest because it
is involved in many vital functions and because of its high
bioavailability. Recently, several prospective studies have
reported the importance of calcium content in fermented
dairy products such as cheese. The effect of calcium may
affect the lipid profile by increasing the excretion of fat in
feces and therefore exert a positive effect on serum lipid
profile (89).
Limitations of the present study
There are some limitations in the present study that need to
be acknowledged. First, some primary observational studies

S184 Supplement
 A
Rideout et al. (2013) (62) − Low Dairy 1.42% 0.70 [−8.02, 9.42]
Rideout et al. (2013) (62) − High Dairy 2.32% −1.20 [−8.04, 5.64]
Drouin−Chartier et al. (2014) (56) − Dairy 14.76% 0.00 [−2.71, 2.71]
Tanaka et al. (2014) (60) − Dairy 11.73% 2.00 [−1.04, 5.04]
Conway et al. (2014) (64) − Buttermilk 6.70% −1.20 [−5.22, 2.82]
Benatar et al. (2014) (65) − Low Dairy 13.03% −1.90 [−4.78, 0.98]
Benatar et al. (2014) (65) − Medium Dairy 12.14% −2.50 [−5.49, 0.49]
Benatar et al. (2014) (65) −High Dairy 12.92% −0.50 [−3.39, 2.39]

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Raziani et al. (2016) (67) − Regular Fat Cheese 8.17% −0.30 [−3.94, 3.34]
Raziani et al. (2016) (67) − Reduced Fat Cheese 8.08% −1.90 [−5.56, 1.76]
Soerensen et al. (2014) (66) − Milk 4.13% −1.40 [−6.52, 3.72]
Soerensen et al. (2014) (66) − Cheese 4.61% −1.20 [−6.05, 3.65]

RE Model 100.00% −0.77 [−1.81, 0.27]

−10 −5 0 5 10

Mean Difference

B
Rideout et al. (2013) (62) − Low Dairy 1.79% −1.20 [−11.07, 8.67]
Rideout et al. (2013) (62) − High Dairy 1.95% −3.80 [−13.24, 5.64]
Drouin−Chartier et al. (2014) (56) − Dairy 21.22% −1.00 [ −3.86, 1.86]
Tanaka et al. (2014) (60) − Dairy 11.53% 2.20 [ −1.68, 6.08]
Conway et al. (2014) (64) − Buttermilk 6.24% −2.60 [ −7.88, 2.68]
Benatar et al. (2014) (65) − Low Dairy 12.66% −1.20 [ −4.91, 2.51]
Benatar et al. (2014) (65) − Medium Dairy 10.94% 0.90 [ −3.09, 4.89]
Benatar et al. (2014) (65) −High Dairy 12.13% 0.10 [ −3.69, 3.89]
Raziani et al. (2016) (67) − Regular Fat Cheese 4.57% 2.00 [ −4.16, 8.16]
Raziani et al. (2016) (67) − Reduced Fat Cheese 4.69% −1.20 [ −7.29, 4.89]
Soerensen et al. (2014) (66) − Milk 4.77% −0.80 [ −6.84, 5.24]
Soerensen et al. (2014) (66) − Cheese 7.52% −2.00 [ −6.81, 2.81]

RE Model 100.00% −0.41 [ −1.73, 0.91]

−15 −10 −5 0 5 10

Mean Difference

FIGURE 11 Forest plot for the updated meta-analysis of randomized controlled trials included from 2013 to 2018 evaluating the
influence of consumption of dairy products on SBP (A) and DBP (B). The effect size and 95% CI for fully adjusted random effects are
depicted for each RCT. Pooled effect estimate is represented by the black diamond. (A) SBP: overall effect Z = −0.61, P = 0.54;
heterogeneity I2 = 0.0% (0.00%, 20.28%) (Q = 4.83, df = 11, P = 0.93); (B) DBP: overall effect Z = −1.45, P = 0.15; heterogeneity I2 = 0.0%
(0.00%, 30.14%) (Q = 6.11, df = 11, P = 0.87). DBP, diastolic blood pressure; RE, random effects; SBP, systolic blood pressure.

were included in most of the selected systematic reviews
and meta-analyses; thus, the influence of those studies is
overstated, although this overlapped evidence comes from
the largest well-designed cohort studies. In addition, the
amount of dairy product consumption for the dose–response
analyses varied across studies; therefore, these results should
be cautiously interpreted. Second, some of the included
systematic reviews and meta-analyses are outdated, so that
they did not include the latest cohort or case control studies,
although our results did not show differences regardless
of the date of publication of the studies. Third, because
the search did not consider gray literature (e.g., research
and project reports, annual or activity reports, theses, or
conference proceedings), we cannot exclude the possibility
that language restrictions and unpublished studies might
modify our results to some extent. Fourth, most meta-
analyses included population-based cohort studies with a
large sample size and number of events, but these cohort
studies were not specifically designed for assessing the
influence of dairy product consumption on the incidence
of CVD events; thus, in some, the identification of the type
of dairy product and the assessment of consumption could
have some inaccuracies. Fifth, although most meta-analyses
reported inverse associations, it is possible that some people
with high consumption of some dairy products (low-fat milk,
yogurt) are prone to being engaged in other healthy lifestyle
behaviors. Sixth, it has been repeatedly recognized that
accurately quantifying dietary intake in noninstitutionalized
populations is a major challenge in nutritional epidemiology.
Seventh, the intake amount could differ greatly between
studies included in the systematic reviews and meta-analyses,
mainly considering the consumption differences between
Western and Eastern countries, and this fact could threaten
the robustness of our findings. In addition, although all the 17

Dairy products and cardiovascular disease S185

meta-analyses included in our review described and analyzed
the issues of heterogeneity (Table 1), the differences among
heterogeneity reported in the included meta-analyses could
affect the interpretation of results. Finally, all the 17 meta-
analyses included in our study analyzed satisfactorily the het-
erogeneity, item 15 of AMSTAR 2, which addresses whether
the meta-analysis’ authors have conducted a satisfactory
investigation of publication bias (small study bias) and have
discussed its likely impact on the results of the review, only 4
meta-analyses did not adequately perform this evaluation.
There is a strong debate over the validity of memory-based
dietary assessment methods utilized in epidemiological
research related to food group consumption and major events
of disease (90, 91). Indeed, well-designed and -conducted
RCTs are useful to determine the potential effects of the
consumption of food products and disease risk. However,
when intervention studies are not feasible, longitudinal
cohorts with an appropriate control of confounding and
based on the use of memory-based dietary assessment
methods become an important tool (92). Anyhow, FFQs
are prone to measurement error: 1) cognitively, the usual
frequency of intake questions are difficult to answer; 2) the
number of foods one can ask about is limited and extensive
detail about food preparation is not collected; 3) FFQs
generally query usual portion size, which may not be so
problematic for discrete foods like pieces of fruit or packaged
foods, but can be quite difficult and highly variable for foods
like cheese, pasta, vegetables, beverages, fish, and meats (93).
Although RCTs provide consistent evidence about the
ability of dietary interventions to affect biomarkers of CVD
because they are free of most biases, we cannot ignore the
fact that they also have several limitations, among which
it is worth mentioning the short duration, which results in
uncertainty concerning any expected change in the incidence
of disease (e.g., CHD events, stroke, etc.); compliance with
the intervention diet usually decreases during an extended
clinical trial; allocation concealment is difficult when the
groups are consuming particular foods; and patients with the
control diet can change their habits to those being treated or
in the intervention group (18).
Conclusions
From the results obtained in this review, it can be affirmed
that the consumption of total dairy products either with
regular- or low-fat content, or with different dose-responses
showed no association with CVD or heart failure; the same
results or lower risk of incidence or mortality were found
for ischemic and hemorrhagic stroke. Moreover, evidence has
been provided of an inverse association of the consumption
of dairy products with the vascular diseases IHD and MI.
There was no association of milk consumption, including
in dose–response studies, or fat content with the different
outcomes, although several relatively minor risks have been
found on CVD or stroke. Cheese, fermented milk, or fer-
mented dairy product intake showed an inverse association
with fatal and nonfatal stroke. It has been reported that
S186 Supplement
consumption of moderate quantities of butter showed no
association with CVD, CHD, or stroke.
In consequence, current evidence from the results ob-
tained in this review supports that consumption of dairy
products does not adversely affect the risk of cardiovascular
outcomes (CVD, CHD, and stroke) and may even have a
subtle protective effect.
Downloaded from https://academic.oup.com/advances/article-abstract/10/suppl_2/S164/5489436 by University of Southern Denmark user on 16 May 2019
The results of the meta-analyses of the RCTs obtained in
the present work confirm that dairy product consumption
does not negatively affect the development of CVD, as
evidenced by the nonadverse effects on risk biomarkers such
as blood pressure (SBP and DBP) and plasma lipids (total
cholesterol and LDL cholesterol).
However, it would be interesting to design new long-term
RCT studies that help to clarify the underlying mechanisms
occurring after intake of milk and dairy products, regardless
of fat content, in relation to cardiovascular health at different
doses and stages of life.
Acknowledgments
We thank our collaborators, especially Celia Álvarez-Bueno
and Augusto Anguita-Ruiz, for their assistance with the
meta-analysis software. All authors read and approved the
final manuscript.
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