Am J Clin Nutr-2011-Soedamah-Muthu-158-71.pdf

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Milk and dairy consumption and incidence of cardiovascular diseases

and all-cause mortality: dose-response meta-analysis of prospectivecohort studies1–3

Sabita S Soedamah-Muthu, Eric L Ding, Wael K Al-Delaimy, Frank B Hu, Marielle F Engberink, Walter C Willett, and Johanna M Geleijnse

ABSTRACT

Background: The consumption of dairy products may influence the

risk of cardiovascular disease (CVD) and total mortality, but con-

flicting findings have been reported.

Objective: The objective was to examine the associations of milk,

total dairy products, and high- and low-fat dairy intakes with the

risk of CVD [including coronary heart disease (CHD) and stroke]and total mortality.

Design: PubMed, EMBASE, and SCOPUS were searched for ar-

ticles published up to February 2010. Of .5000 titles evaluated, 17

met the inclusion criteria, all of which were original prospective

cohort studies. Random-effects meta-analyses were performed with

summarized dose-response data. Milk as the main dairy product was

pooled in these analyses.

Results: In 17 prospective studies, there were 2283 CVD, 4391

CHD, 15,554 stroke, and 23,949 mortality cases. A modest inverse

association was found between milk intake and risk of overall CVD

[4 studies; relative risk (RR): 0.94 per 200 mL/d; 95% CI: 0.89,

0.99]. Milk intake was not associated with risk of CHD (6 studies;

RR: 1.00; 95% CI: 0.96, 1.04), stroke (6 studies; RR: 0.87; 95% CI:0.72, 1.05), or total mortality (8 studies; RR per 200 mL/d: 0.99;

95% CI: 0.95, 1.03). Limited studies of the association of total dairy

products and of total high-fat and total low-fat dairy products (per

200 g/d) with CHD showed no significant associations.

Conclusion: This dose-response meta-analysis of prospective stud-

ies indicates that milk intake is not associated with total mortality

but may be inversely associated with overall CVD risk; however,

these findings are based on limited numbers. Am J Clin Nutr

2011;93:158–71.

INTRODUCTION

Cardiovascular disease (CVD) is the main cause of death in the

Western world, claiming 17 million lives per year (1). The burden

from coronary heart disease (CHD) as its main component is

projected to rise from ’47 million disability-adjusted life-years

in 1990 (DALY = healthy years of life lost) to 82 million DALYs

in 2020 (1). It has been postulated that the consumption of dairy

products influences the risk of CVD (including CHD and stroke)

or all-cause mortality, but findings from epidemiologic studies

have been conflicting. Several prospective cohort studies have

suggested inverse associations of milk in particular with stroke

(2–5), but also with CHD (3) and all-cause mortality (6).

Whereas other cohort studies reported that milk was positively

associated with CHD (7) or stroke (8). Many studies also re-

ported no significant association between milk and CHD (9–13),

stroke (14, 15), or all-cause mortality (16–19). Total dairy intake

was rarely reported (compared with milk) and yielded conflict-

ing evidence, with no relation to CHD (20, 21). Meanwhile,

high-fat dairy product consumption has been shown to be pos-

itively related to CHD (22, 23), whereas low-fat dairy product

consumption has been shown to be inversely associated with

CHD (22) or stroke (15).

The mechanisms by which dairy products can exert certain

effects on CVD are diverse, with divergent mechanisms sug-

gesting both positive and negative influences. Dairy products are

rich in minerals (calcium, potassium, and magnesium), protein

(casein and whey), and vitamins (riboflavin and vitamin B-12)

that can exert beneficial effects on CVD. On the other hand,

saturated fat in dairy products can adversely influence CHD,

although the effect of saturated fat on CHD risk depends on the

source of calories (unsaturated fatty acids or carbohydrates) by

which it is substituted to maintain energy balance (24). There is

some suggestion that low-fat dairy products may beneficially

influence blood pressure (25, 26). Studies have shown that the

Dietary Approaches to Stop Hypertension (DASH) dietary

pattern—which is high in fruit, vegetables, nuts, fish, and low-fat

dairy products—lowers blood pressure effectively, which may in

part be attributed to its relatively high content of low-fat dairy

products (27). Whether these effects on blood pressure can be

specifically addressed by low-fat dairy products is not clear from

1From the Division of Human Nutrition, Wageningen University,

Wageningen, Netherlands (SSS-M, MFE, and JMG); the Department of

Nutrition and Epidemiology, Harvard School of Public Health, Boston,MA (ELD, FBH, and WCW); the Channing Laboratory, Department of

Medicine, Brigham and Women’s Hospital and Harvard Medical School,

Boston, MA (ELD, FBH, and WCW); and the Department of Family and

Preventive Medicine, University of California, San Diego, San Diego, CA

(WKA-D).2

Supported by an unrestricted grant from the Dutch Dairy Association (to

SSS-M and JMG).3 Address correspondence and requests for reprints to SS Soedamah-Muthu,

Division of Human Nutrition, Wageningen University, PO Box 8129, 6700 EV

Wageningen, Netherlands. E-mail: [email protected].

Received May 25, 2010. Accepted for publication September 30, 2010.

First published online November 10, 2010; doi: 10.3945/ajcn.2010.29866.

158 Am J Clin Nutr 2011;93:158–71. Printed in USA. 2011 American Society for Nutrition

b y g u e s t on O c t o b er 8 ,2 0 1 2

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29866.DC1.htmlhttp://ajcn.nutrition.org/content/suppl/2010/12/20/ajcn.2010.Supplemental Material can be found at:

http://ajcn.nutrition.org/http://ajcn.nutrition.org/http://ajcn.nutrition.org/http://ajcn.nutrition.org/http://ajcn.nutrition.org/http://ajcn.nutrition.org/http://ajcn.nutrition.org/http://ajcn.nutrition.org/http://ajcn.nutrition.org/http://ajcn.nutrition.org/http://ajcn.nutrition.org/http://ajcn.nutrition.org/http://ajcn.nutrition.org/http://ajcn.nutrition.org/http://ajcn.nutrition.org/http://ajcn.nutrition.org/http://ajcn.nutrition.org/http://ajcn.nutrition.org/http://ajcn.nutrition.org/http://ajcn.nutrition.org/http://ajcn.nutrition.org/


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DASH, but European guidelines on CVD prevention do rec-

ommend the DASH diet with low-fat dairy products, albeit such

a recommendation is not yet fully evidence-based (28). Two

meta-analyses (29, 30) and 2 narrative reviews (31, 32) combined

with individual studies produced conflicting conclusions. Com-

bining evidence from different study designs (ecologic, case-

control, and prospective) and different study populations (age,

sex, country, and various mean milk intakes) may explain the

conflicting results. Pooling different exposures (calcium andmilk) and the use of inappropriate statistical methods could also

lead to conflicting conclusions.

Therefore, we conducted a new systematic evaluation of the

association between intakes of milk, total dairy products, total

high-fat dairy products, and total low-fat dairy products with risk

of total CVD, CHD, stroke, and all-cause mortality via a dose-

response meta-analysis of prospective cohort studies in healthy

adult men and women.

SUBJECTS AND METHODS

Study selection for the meta-analysisA systematic literature review was conducted by using the data-

bases PubMed (http://www.ncbi.nlm.nih.gov/pubmed), EMBASE

(http://www.embase.com), and SCOPUS (http://www.scopus.com)

from 10 February 2009 until 1 June 2009, based on the query

syntax shown in supplemental Table 1 (see “Supplemental data”

in the online issue ). An updated secondary search was con-

ducted until 22 February 2010. First, titles of the articles were

screened, on basis of which we excluded animal studies, chil-

dren aged ,18 y, and diseased populations (including diabetes

and CVD). Second, abstracts of the articles were screened for the

following inclusion criteria: prospective cohort studies, original

articles, general population, dairy products as main exposure, and

fatal or nonfatal CVD (CHD and stroke) or mortality outcomes.For articles that met the inclusion criteria, the full text was re-

trieved. An additional hand search for relevant articles was per-

formed by using bibliographies of scientific articles (eg, review

articles).

Dairy intake data as well as relative risks (RRs) for CVD,

CHD, stroke, and all-cause mortality (with 95% CIs) were

extracted from the selected articles. If insufficient data were

reported in the article (eg, absence of RRs, CIs, dairy intakes, or

number of cases), additional information was requested from the

authors (7, 14, 20–22). All data were extracted into a predefined

spreadsheet and checked several times. The selection and data

extraction process was executed by 2 independent reviewers

(SSS-M and JMG). If multiple articles were on the same studysample with the same exposure and outcome [Caerphilly cohort

study (4, 10), Iowa Women’s Health study (9, 23)], only the

publication with the largest number of outcome cases was

retained. In one study population (Oxford Vegetarian Study) (7,

11), because different outcomes were reported in different arti-

cles, both articles on the same study population were included.

Main outcomes

Outcomes in this study included incident major CVD (fatal and

nonfatal CHD and stroke), CHD (fatal and nonfatal), stroke (fatal

and nonfatal), and all-cause mortality, defined as such in the

underlying studies. CVD was defined as CHD or stroke [WHO

International Classification of Diseases (ICD)-10 I60-69; http://

www.who.int/classifications/icd/en] and other CVD, including

cardiac arrest (I46), heart failure (I50), and sudden death (R96).

CHD was defined as acute myocardial infarction, angina pec-

toris, and other ischemic heart disease (as in ICD-10 I20-I25).

Statistical methodsDairy intakes were converted from servings or other units into

g/d by using standard conversions from the Food Standards

Agency (pint = 585 g; milk, 1 glass = 200 mL; and total dairy =

200 g) (33, 34). Assumptions were made to convert all dairy

exposure data into g/d or for milk into mL/d. For this 1 serving,

dairy products or milk were estimated to be on average 200 g or

200 mL, respectively.

We examined the association between milk consumption and

CVD, CHD, stroke, and all-cause mortality. Because there were

insufficient numbers of studies for dairy products and outcomes

other than CHD, we analyzed total dairy, total low-fat dairy, and

total high-fat dairy products only for CHD risk. There were

insufficient numbers of studies (2) including certain exposures,such as cheese, yogurt, and high-fat or low-fat milk; therefore,

these analyses could not be pursued.

Only studies with similar exposures and outcomes were pooled

to avoid heterogeneity, according to a predefined data-analysis plan.

We used STATAversion 11.0 (StataCorp, College Station, TX)

for meta-analysis using the METAN command, whereas dose-

response meta-analyses were conducted by using the GLST

command with the generalized least-squares method for trend

estimation of summarized dose-response data, based on the

Greenland and Longnecker method (35). All statistical tests

were 2-sided with a = 0.05. Restricted cubic splines were used to

assess for potential curvilinear relations.

Between-study heterogeneity was assessed via the I 2 statistic(36), which expresses the percentage of variation attributable to

between-study heterogeneity. Random-effects pooling were con-

ducted by using DerSimonian and Laird random-effects models

(37). Forest plots were made for the relation between milk or

dairy and CVD, CHD, stroke, and all-cause mortality. From each

publication, we used the results from the main multivariable

model that included most confounders. Subgroup analyses were

performed by sex, age (young compared with old), continent, and

degree of adjustment for confounding, providing sufficient num-

bers of studies. For year of publication and BMI, variation was

insufficient across studies to conduct subgroup analyses. To assess

whether studies of lesser quality could have influenced the results,

meta-analyses were split by categorizing studies by whether ornot they adjusted for the most essential confounders (age, sex,

BMI, smoking, and total energy intake). Most of the associations

were not adjusted for physical activity or other aspects of diet,

including intakes of fruit and vegetables and specific fatty acids;

therefore, these could not be included.

To explore heterogeneity with a statistical test, further meta-

regression analyses were performed to relate the size of effect to

one or more characteristics (age, sex, and confounder adjustments)

of the studies involved. In addition, interaction terms were added,

and statistical significance was evaluated. For the analysis on total

mortality, which included most studies (n = 8), we used a funnel

plot to assess the presence of publication bias. In addition, we

DAIRY AND CVD META-ANALYSIS 159



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tested for publication bias with the Begg’s test (38). A spaghetti

plot, developed by Ding (ELD), was used to illustrate the di-

rection of the association between milk and all-cause mortality.

RESULTS

Study populations

We identified a total of 87 articles from PubMed, 40 from

EMBASE, and 22 from SCOPUS (Figure 1). In the full-text

stage, we narrowed the number of studies from 27 to 17 after

applying our search criteria. Nine studies were excluded because

of insufficient data on dairy intakes or if RRs or 95% CIs could

not be extracted (2, 12, 13, 19, 39–43). One study (23) was

excluded because the same analyses were already included in an

earlier larger study of the same population (9). A total of 17

studies were included, the study characteristics of which are

presented in Table 1 (3, 5–11, 14–18, 20–22, 44). The mean (6

SD) age of the study populations included was 56 6 13 y (range:

34–80 y) for a total of 611,430 participants across 17 studies,

and the mean (6 SD) duration of follow-up was 14.0 6 6.0 y.

Five studies were conducted in the United States, 2 in Japan, and

10 in Europe. The mean BMI (in kg/m2) was 25, as reported in

11 (65%) studies. The studies were pooled to assess milk intake

according to the outcomes: 8 studies on all-cause mortality, 6

studies on CHD, 6 studies on stroke, and 4 studies on CVD

outcomes (see supplemental Table 2 under “Supplemental data”

in the online issue). The intake range for milk across all studies

was 0–850 mL/d, with a mean (6 SD) intake of 266 6 210 mL/d.

For total dairy products and CHD, 4 studies were pooled; for total

high-fat dairy products and CHD, 4 studies were pooled; and for

total low-fat dairy products and CHD, 3 studies were pooled (see

supplemental Table 3 under “Supplemental data” in the online

issue). The mean (6 SD) intake for total dairy products across the

4 studies was 419 6 215 g/d (range: 114–828 g/d).

Total CVD

Data from a total of 13,518 participants and 2283 CVD (fatal

and nonfatal) cases were analyzed in 4 prospective cohort studies,

with milk as the main exposure. The mean (6SD) age was 55 6

8 y. Two studies comprised only men, and 2 studies had a similar

distribution of men and women; the mean (6 SD) follow-up was

16 6 9 y. The mean (6SD) milk intake across these 4 studies

was 313 6

214 mL/d. Pooled results indicated an inverse as-sociation between milk and total CVD risk (RR: 0.94; 95% CI:

0.89, 0.99) per glass (200 mL/d) (Figure 2), with no evidence of

between-study heterogeneity ( I 2 = 0%, P = 0.5). From a strati-

fied analysis, effect-modification heterogeneity was suggestive

for sex and degree of confounding, albeit not statistically sig-

nificant (P for interaction . 0.05). An inverse association be-

tween milk and CVD was shown in studies that included only

men (RR: 0.93; 95% CI: 0.87, 0.99), and no association was

shown in studies that included both men and women (RR: 1.10;

95% CI: 0.67, 1.80). By degree of confounding, studies that used

full adjustment showed an inverse association between milk and

CVD (RR: 0.94; 95% CI: 0.88, 1.01), whereas studies that did

not use full adjustment showed no association (RR: 1.10; 95%CI: 0.66, 1.84).

CHD

Data from a total of 259,162 participants and 4391 CHD

(fatal and nonfatal) cases were analyzed in 6 prospective cohort

studies, with milk as the main exposure. The mean (6SD) age

was 50 6 11 y. Three studies included only men, 2 studies

included 40% men and 60% women, and 1 study included

only women; the mean (6SD) follow-up was 16 6 6 y. The

mean milk intake was 263 mL/d (range: 0–659 mL/d) for these

6 studies. The pooled results from these 6 studies (Figure 3)

with CHD outcomes suggested no association between milk

FIGURE 1. Flow chart of the meta-analysis of dairy product consumption and incident cardiovascular disease (CVD) and all-cause mortality. The numbersof studies retrieved from 3 electronic databases [PubMed (http://www.ncbi.nlm.nih.gov/pubmed), EMBASE (http://www.embase.com), and SCOPUS (http://

www.scopus.com)] are shown. Each box contains the number of studies found. The steps from title to abstract to full-text screening are indicated, as are theinclusion and exclusion criteria. Hand searches are indicated separately from the electronic search.

160 SOEDAMAH-MUTHU ET AL



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T A B L E

1

C h a r a c t e r i s t i c s o f 1 7 p r o s p e c t i v e c o h o r t s t u d i e s o n d a i r y p r o d u c t s a n d m i l k c o n s u m p t i o n

a n d c a r d i o v a s c u l a r d i s e a s e ( C V D ) a n d a l l - c a u s e m o r t a l i t y e v e n t s 1

R e f e r e n c e

S t u d y , c o u n t r y

P e r c e n t a g e

o f m

e n /

w o m

e n

M e a n a g e

F o l l o w -

u p t i m e

N o . o f

s u b j e c t s

N o . o f c a s e s

R e s u l t s

a v a i l a b l e 2

E x p o s u r e 3

Y e a r

d i e t a r y d a t a

c o l l e c t e d

O u t c o m e

M a i n c o n f o u n d e r s

%

y

y

A p p l e b y e t a l ,

1 9 9 9 ( 7 )

O x f o r d

V e g e t a r i a n

S t u d y , U K

3 8 / 6 2

3 4

1 2

1 0 , 8 0 0

6 3 d e

a t h s

f r o m C H D

M i l k a n d

c h e e s e

a n d f a t a l

C H D ;

R R ( 9 5 %

C I )

S i m p l e F F Q ( n o

t

v a l i d a t e d ) ;

m i l k :

3 c a t e g o r i e s

( p i n t s / d ) ;

c h e e s e :


( f r e q u e n c y /

w k )

1 9 8 4

F a t a l C H D c o l l e c t e d

f r o m n a t i o n a l

r e g i s t r y d e a t h

c e r t i fi c a t e s , I C D

c o d e d

A g e , s e x , s m o k i n g ,

s o c i o e c o n o m i c

s t a t u s

B o s t i c k e t a l ,

1 9 9 9 ( 9 )

P o s t m e n o p a u s a l

w o m e n , I o w a ,

U S A

0 / 1 0 0

6 1 . 5

8

3 4 , 4 8 6

3 8 7

T o t a l d a i r y

a n d h i g h - f a t

d a i r y a n d

f a t a l

C H D ; R R

( 9 5 % C I )

F F Q ( v a l i d a t e d ) ;

d a i r y

p r o d u c t s :


( u n i t s / d ) ; f a t -

c o n t a i n i n g

d a i r y

p r o d u c t s :


( s e r v i n g s / w k ) ;

d e fi n e d a s

m i l k

p r o d u c t s ,

e x c l u d i n g

b u t t e r

1 9 8 6

F a t a l C H D c o l l e c t e d

f r o m r e g i s t r y a n d

f o l l o w - u p

q u e s t i o n n a i r e s ,

I C D c o d e d , n o t

v a l i d a t e d

A g e , t o t a l e n e r g y

i n t a k e , B M I , W H R ,

h i s t o r y o f D M ,

s m o k i n g , e s t r o g e n ,

a l c o h o l , e d u c a t i o n ,

m a r i t a l s t a t u s ,

p h y s i c a l a c t i v i t y ,

v i t a m i n E , s a t u r a t e d

f a t i n t a k e

E l w o o d e t a l ,

2 0 0 4 ( 1 0 )

C a e r p h i l l y

c o h o r t ,

m e n , S o u t h

W a l e s , U K

1 0 0 / 0

5 2

2 2

2 5 1 2

4 9 3 C

H D , 1 8 5

s t r o k e , 8 1 1

d e a

t h s

M i l k a n d

s e v e r a l

o u t c o m e s

( f a t a l a n d

n o n f a t a l

C H D ,

n o n f a t a l

s t r o k e ,

f a t a l a n d

n o n f a t a l

C V D ,

d e a t h ) ; R R

( 9 5 % C I )


m i l k : 4

c a t e g o r i e s

( p i n t s / d )

1 9 8 3

F a t a l a n d n o n f a t a l

C H D a n d C V D ,

s t r o k e , a n d a l l -

c a u s e m o r t a l i t y ;

e x a m i n a t i o n b y

E C G , G P +

h o s p i t a l r e c o r d s

w e r e u s e d , I C D

c o d e d

A g e , t o t a l e n e r g y ,

s m o k i n g , s o c i a l

c l a s s , B M I , s y s t o l i c

B P , a l c o h o l a n d f a t ,

p r i o r v a s c u l a r

d i s e a s e

( C o n t i n u e d )




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T A B L E

1


R e f e r e n c e


P e r c e n t a g e

o f m

e n /

w o m

e n

M e a n a g e

F o l l o w -

u p t i m e

N o . o f

s u b j e c t s

N o . o f c a s e s

R e s u l t s

a v a i l a b l e 2

E x p o s u r e 3

Y e a r


c o l l e c t e d

O u t c o m e


%

y

y

F o r t e s e t a l ,

2 0 0 0 ( 6 )

E l d e r l y r e s i d e n t s

f r o m p u b l i c

h o m e ,

R o m e , I t a l y

3 2 / 6 8

8 0

5

1 6 2

5 3 d e

a t h s

M i l k a n d

y o g u r t a n d

a l l - c a u s e

m o r t a l i t y ;

R R ( 9 5 % C I )


m i l k a n d

y o g u r t

( f r e q u e n c y / w k )

1 9 9 3

A l l - c a u s e m o r t a l i t y ,

c o l l e c t e d f r o m

r e g i s t r y , n o c a u s e

o f d e a t h

A g e , s e x , e d u c a t i o n ,

B M I , s m o k i n g ,

c o g n i t i v e f u n c t i o n ,

c h r o n i c d i s e a s e s

H u e t a l ,

1 9 9 9 ( 2 2 )

N u r s e s ’ H e a l t h

s t u d y , f e m a l e

r e g i s t e r e d

n u r s e s

i n 1 1 s t a t e s ,

U S A

0 / 1 0 0

4 6 . 5

1 4

4 1 , 2 5 4

9 3 9

T o t a l , h i g h - ,

a n d l o w - f a t

d a i r y a n d

m i l k a n d

f a t a l

a n d

n o n f a t a l

C H D ; R R

( 9 5 % C I )


t o t a l , h i g h - ,

a n d l o w - f a t d a i r y

p r o d u c t s a n d

m i l k :


( s e r v i n g s / d )

1 9 8 0

N o n f a t a l M I + f a t a l

C H D b y m e d i c a l

r e c o r d s r e v i e w e d

b y p h y s i c i a n s

b l i n d t o r i s k

f a c t o r s ; d e a t h s

f r o m r e g i s t r y ,

h o s p i t a l r e c o r d s ,

a u t o p s y r e p o r t s

A g e , t i m e p e r i o d ,

B M I , s m o k i n g ,

m e n o p a u s a l s t a t u s

( i n c l u d i n g h o r m o n e

r e p l a c e m e n t

t h e r a p y ) , p a r e n t a l

h i s t o r y o f M I ,

v i t a m i n E

s u p p l e m e n t ,

a l c o h o l , h i s t o r y o f

h y p e r t e n s i o n ,

a s p i r i n , p h y s i c a l

a c t i v i t y , t o t a l e n e r g y

i n t a k e

I s o e t a l ,

1 9 9 9 ( 1 4 )

N u r s e s ’ H e a l t h

s t u d y , f e m a l e

r e g i s t e r e d

n u r s e s

i n 1 1 s t a t e s ,

U S A

0 / 1 0 0

4 6

1 4

8 5 , 7 6 4

3 4 7

M i l k , l o w -

f a t a n d

h i g h - f a t

m i l k ,

y o g u r t ,

c h e e s e ,

a n d r i s k o f

f a t a l a n d

n o n f a t a l

s t r o k e ; R R

( 9 5 % C I )

F F Q ( v a l i d a t e d ) ,


f o r y o g u r t ( 5

t i m e s / w k ) ,

c h e e s e

( 1 t i m e / d ) ,

m i l k ( 2

t i m e s / d )

1 9 8 0


s t r o k e b y

q u e s t i o n n a i r e ,

m e d i c a l r e c o r d s

( r e v i e w e d b l i n d ) ,

a n d d e a t h

c e r t i fi c a t e s

A g e , s m o k i n g , t i m e

p e r i o d , B M I ,

a l c o h o l ,

m e n o p a u s a l s t a t u s

( i n c l u d i n g h o r m o n e

r e p l a c e m e n t

t h e r a p y ) , p h y s i c a l

a c t i v i t y ,

m u l t i v i t a m i n u s e ,

v i t a m i n E

s u p p l e m e n t a t i o n ,

h i s t o r y o f


D M , a n d

h y p e r c h o l e s t e r o l e m i a





D o




6/14

T A B L E

1


R e f e r e n c e


P e r c e n t a g e

o f m

e n /

w o m

e n

M e a n a g e

F o l l o w -

u p t i m e

N o . o f

s u b j e c t s

N o . o f c a s e s

R e s u l t s

a v a i l a b l e 2

E x p o s u r e 3

Y e a r


c o l l e c t e d

O u t c o m e


%

y

y

K a h n e t a l ,

1 9 8 4 ( 1 7 )

C a l i f o r n i a

S e v e n t h -

d a y A d v e n t i s t

g r o u p

c o m p a r e d

w i t h n o n -

A d v e n t i s t s ,

U S A

4 0 / 6 0

—

2 1

2 7 , 5 3 0

6

0 0 0

C h e e s e a n d

m i l k a n d

a l l - c a u s e

m o r t a l i t y ;

R R ( 9 5 % C I )

Q u e s t i o n n a i r e

( n o t v a l i d a t e d ) ;

m i l k :


( g l a s s e s / d ) ;

c h e e s e :


( d a y s / w k )

1 9 6 0


8 5 % o f d e a t h s

w e r e m a t c h e d b y

c o m p u t e r t a p e s o f

l o c a l r e g i s t r y , n o

c a u s e o f d e a t h ,

n o g o o d

v a l i d a t i o n


h i s t o r y o f c h r o n i c

d i s e a s e s

K i n j o e t a l ,

1 9 9 9 ( 5 )

J a p a n e s e

p r e f e c t u r e

s t u d y , J a p a n

5 6 / 4 4

5 5

1 5

2 2 3 , 1 7 0

1 1

, 0 3 0

M i l k a n d

f a t a l

s t r o k e ; R R

( 9 5 % C I )

O n e - p a g e

q u e s t i o n n a i r e

( n o t w e l l

a s s e s s e d m i l k

d a t a ) ; m i l k :



w k )

1 9 6 5

F a t a l s t r o k e , d e a t h s

a s c e r t a i n e d b y

v i t a l s t a t i s t i c s ,

c o d e d c a u s e o f

d e a t h

S e x , a t t a i n e d a g e ,

f o l l o w - u p , p r e f e c t u r e

( = u n i t o f

a d m i n i s t r a t i o n o r

c o u n t y i n C h i n a ) ,

a l c o h o l , s m o k i n g ,

o c c u p a t i o n

K n o o p s e t a l ,

2 0 0 6 ( 1 6 )

H A L E s t u d y

( c o m b i n a t i o n

o f S E N E C A

a n d F I N E s t u d i e s ) ,

E u r o p e

6 6 / 3 4

7 5

1 0

3 1 1 7

1

3 8 2

M i l k a n d

m i l k

p r o d u c t s

a n d a l l -

c a u s e

m o r t a l i t y ;

R R ( 9 5 %

C I )

D i e t a r y h i s t o r y ,

f o o d d u r i n g

1 m o

i n S E N E C A

S t u d y , 2 – 4 w k

i n F I N E S t u d y ;

v a l i d a t e d

m e t h o d s ;

c o n t i n u o u s

v a r i a b l e

( i n g / d )

1 9 8 8

A l l - c a u s e m o r t a l i t y

a s c e r t a i n e d b y

v i t a l s t a t i s t i c s ,

I C D - c o d e d c a u s e

o f d e a t h , d e a t h

c e r t i fi c a t e s , o r

m e d i c a l d o c t o r

A g e , s e x , a l c o h o l ,


s m o k i n g , n u m b e r o f

y e a r s o f e d u c a t i o n ,

B M I , c h r o n i c d i s e a s e s

a t b a s e l i n e , c e n t e r

L a r s s o n e t a l ,

2 0 0 8 ( 8 )

W i t h i n t h e

A l p h a -

T o c o p h e r o l ,

B e t a -

C a r o t e n e

C a n c e r

P r e v e n t i o n

S t u d y ,

F i n l a n d

1 0 0 / 0

5 7

1 3 . 6

2 6 , 5 5 6

2

7 0 2

T o t a l d a i r y

p r o d u c t s ,

l o w - f a t

m i l k ,

w h o l e

m i l k ,

y o g u r t ,

c h e e s e ,

a n d f a t a l

a n d

n o n f a t a l

s t r o k e ; R R

( 9 5 % C I )


i n t a k e ( g / d ) i n

q u i n t i l e s

1 9 8 8


s t r o k e d a t a

c o l l e c t e d b y

r e c o r d l i n k a g e

w i t h h o s p i t a l

d i s c h a r g e r e g i s t e r

a n d r e g i s t e r f o r

c a u s e s o f d e a t h ;

a g r e e m e n t w a s

c h e c k e d

A g e , s u p p l e m e n t a t i o n

g r o u p , e d u c a t i o n ,

s m o k i n g , B M I , t o t a l

c h o l e s t e r o l , s e r u m

H D L , h i s t o r y o f D M

a n d h e a r t d i s e a s e ,


t o t a l e n e r g y , a l c o h o l ,

c a f f e i n e , s u g a r , r e d

m e a t , p o u l t r y , fi s h ,

f r u i t , j u i c e , v e g e t a b l e s ,

p o t a t o e s , w h o l e g r a i n ,

r e fi n e d g r a i n ( C

o n t i n u e d )




D o




7/14

T A B L E

1


R e f e r e n c e


P e r c e n t a g e

o f m

e n /

w o m

e n

M e a n a g e

F o l l o w -

u p t i m e

N o . o f

s u b j e c t s

N o . o f c a s e s

R e s u l t s

a v a i l a b l e 2

E x p o s u r e 3

Y e a r


c o l l e c t e d

O u t c o m e


%

y

y

M a n n e t a l ,

1 9 9 7 ( 1 1 )

V e g e t a r i a n

p a r t i c i p a n t s

a n d

n o n v e g e t a r i a n

c o n t r o l s , U K

3 8 / 6 2

3 4

1 3 . 3

1 0 , 8 0 2

3 9 2

M i l k a n d

c h e e s e

a n d

m o r t a l i t y ;

R R ( 9 5 % C I )

F F Q ( n o t

v a l i d a t e d ) ;

m i l k ( p i n t s / d ) ;

c h e e s e


w k ) i n t e r t i l e s

1 9 8 1


c o l l e c t e d w i t h

O f fi c e f o r

N a t i o n a l

S t a t i s t i c s a n d

c o d e d b l i n d e d


s o c i a l c l a s s

N e s s e t a l ,

2 0 0 1 ( 3 )

S c o t t i s h w o r k i n g

m e n , U K

1 0 0 / 0

4 8

2 5

5 7 6 5

2 3 5 0

d e a t h s ,

8 9 2 d e a

t h s

f r o m C H

D

M i l k a n d

m o r t a l i t y

( a l l - c a u s e ,

C V D

a n d C H D ,

s t r o k e

d e a t h

s e p a r a t e d ) ;

R R ( 9 5 %

C I )


( c h e c k e d b y

i n t e r v i e w ) ;

m i l k ( p i n t s / d =

0 . 5 8 6 L ) i n

t e r t i l e s

1 9 7 3


f a t a l C H D , f a t a l

C V D , a n d f a t a l

s t r o k e c o l l e c t e d

w i t h O f fi c e f o r

N a t i o n a l

S t a t i s t i c s

A g e , s m o k i n g , B P ,

c h o l e s t e r o l , B M I ,

f o r c e d e x p i r a t o r y

v o l u m e , s o c i a l c l a s s ,

e d u c a t i o n ,

d e p r i v a t i o n , s i b l i n g s ,

c a r u s e r , a n g i n a ,

E C G i s c h e m i a ,

b r o n c h i t i s , a l c o h o l

P a g a n i n i - H i l l

e t a l , 2 0 0 7

( 1 8 )

L e i s u r e W o r l d

C o h o r t S t u d y ,

C a l i f o r n i a ,

U S A

3 7 / 6 3

7 4

2 3

1 3 , 6 2 4

1 1 , 3 8 6

M i l k a n d

m o r t a l i t y ;

R R ( 9 5 %

C I )


( n o t v a l i d a t e d ) ;

m i l k ( g l a s s e s / d ) i n

q u a r t i l e s

1 9 8 1


v i t a l s t a t u s b y

d e a t h c e r t i fi c a t e s ,

h o s p i t a l

d i s c h a r g e d a t a


e x e r c i s e , B M I ,

a l c o h o l ,

h y p e r t e n s i o n , a n g i n a ,

M I , s t r o k e , d i a b e t e s ,

r h e u m a t o i d a r t h r i t i s ,

c a n c e r

S a u v a g e t

e t a l , 2 0 0 3

( 1 5 )

L i f e S p a n S t u d y ,

J a p a n

3 8 / 6 2

5 6

1 6

3 1 , 8 3 2

1

0 9 4

M i l k a n d

d a i r y

p r o d u c t s

a n d f a t a l

s t r o k e ; R R

( 9 5 % C I )


m i l k a n d

d a i r y p r o d u c t s

( b u t t e r a n d

c h e e s e )

( f r e q u e n c y / w k )

i n q u a r t i l e s

1 9 7 9

F a t a l s t r o k e , l i n k a g e t o

r e g i s t r a t i o n , d e a t h

c e r t i fi c a t e s , t r a i n e d

c o d e r s , I C D

A g e , s e x , c i t y , r a d i a t i o n

d o s e , B M I , s m o k i n g ,

a l c o h o l , e d u c a t i o n ,

h i s t o r y o f d i a b e t e s ,

o r h y p e r t e n s i o n

P a n a g i o t a k o s

e t a l , 2 0 0 9

( 2 0 )

A T T I C A S t u d y ,

G r e e c e

5 0 / 5 0

5 3

5

6 8 6

3 0

D a i r y p r o d u c t s ,

m i l k ,

c h e e s e ,

y o g u r t , a n d

m i l k a n d

f a t a l a n d

n o n f a t a l

C V D ; R R

( 9 5 % C I )


d a i r y , m i l k ,

c h e e s e ,

y o g u r t i n

t e r t i l e s

( s e r v i n g s / d )

2 0 0 2


C V D , m e d i c a l

r e c o r d s

A g e , s e x , B M I ,


d i a b e t e s ,

h y p e r c h o l e s t e r o l e m i a ,

c u r r e n t s m o k i n g ,

p h y s i c a l a c t i v i t y





D o




8/14

T A B L E

1


R e f e r e n c e


P e r c e n t a g e

o f m

e n /

w o m

e n

M e a n a g e

F o l l o w -

u p t i m e

N o . o f

s u b j e c t s

N o . o f c a s e s

R e s u l t s

a v a i l a b l e 2

E x p o s u r e 3

Y e a r


c o l l e c t e d

O u t c o m e


%

y

y

A l D e l a i m y

e t a l , 2 0 0 3

( 2 1 )

H e a l t h P r o f e s s i o n a l s

F o l l o w - U p

S t u d y , U S A

1 0 0

/ 0

5 3

1 2

1 9 4 , 2 7 6

1 4 4 6 8

T o t a l , h i g h -

f a t , a n d

l o w - f a t

d a i r y

p r o d u c t s

a n d m i l k

a n d f a t a l

a n d

n o n f a t a l

C H D ;

R R ( 9 5 %

C I )

F F Q ( v a l i d a t e d ) ,

d a i r y

p r o d u c t s

( m i l k , y o g u r t ,

i c e - c r e a m ,

a n d c h e e s e )

i n q u i n t i l e s

( s e r v i n g s / d )

1 9 8 6


C H D , m e d i c a l

r e c o r d s r e v i e w e d ,

a u t o p s y r e p o r t s ,

d e a t h c e r t i fi c a t e s

A g e , t i m e p e r i o d ,

e n e r g y i n t a k e ,

h i s t o r y o f d i a b e t e s ,

h i s t o r y o f

h y p e r c h o l e s t e r o l e m i a ,

f a m i l y h i s t o r y o f M I ,

s m o k i n g , a s p i r i n ,

B M I , a l c o h o l i n t a k e ,


v i t a m i n E , t r a n s f a t t y

a c i d s , P U F A : S F A

r a t i o , t o t a l p r o t e i n

i n t a k e , fi b e r , f o l a t e ,

o m e g a - 3 ( n 2 3 ) f a t t y

a c i d s , a n d a - l i n o l e n i c

a c i d

E n g b e r i n k

e t a l , 2 0 0 9 ,

a b s t r a c t

( 4 4 )

R o t t e r d a m

E R G O

S t u d y ,

N e t h e r l a n d s

2 7 / 6 3

6 7

1 1

4 6 6 4

5 5 8

T o t a l h i g h

a n d l o w -

f a t d a i r y

p r o d u c t s ,

m i l k , a n d

c h e e s e a n d

f a t a l

a n d

n o n f a t a l

C H D , f a t a l

C V D ,

a l �

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