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Milk and Dairy Foods: Their Functionality in Human Health and Disease

Milk and Dairy Foods: Their Functionality in Human Health and Disease

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Milk and Dairy Foods: Their Functionality in Human Health and Disease

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861 pagine
10 ore
Pubblicato:
Apr 8, 2020
ISBN:
9780128156049
Formato:
Libro

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Milk and Dairy Foods: Their Functionality in Human Health and Disease addresses issues at key life stages, presenting updates on the impact of dairy on cardiometabolic health, hemodynamics, cardiovascular health, glycemic control, body weight, bone development, muscle mass and cancer. The book also explores the impact of dairy fats on health, dairy fat composition, trans-fatty acids in dairy products, the impact of organic milk on health, milk and dairy intolerances, and dairy as a source of dietary iodine.

Written for food and nutrition researchers, academic teachers, and health professionals, including clinicians and dietitians, this book is sure to be a welcomed resource for all who wish to understand more about the role of dairy in health.

  • Addresses the functional effects of dairy related to reducing the risk of key chronic diseases
  • Contains information related to various life stages, including chapters on dairy foods and bone development in the young and dairy foods and maintenance of muscle mass in the elderly
Pubblicato:
Apr 8, 2020
ISBN:
9780128156049
Formato:
Libro

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Chapter 1

Dairy consumption and cardiometabolic diseases: Evidence from prospective studies

Sabita S. Soedamah-Muthua,b; Jing Guob    a Center of Research on Psychological and Somatic disorders (CORPS), Department of Medical and Clinical Psychology, Tilburg School for Social and Behavioral Sciences, Tilburg University, Tilburg, The Netherlands

b Institute for Food, Nutrition and Health, University of Reading, Reading, United Kingdom

Abstract

Dairy foods are widely recommended in dietary guidelines of several countries, are heterogeneous in type, and contain both beneficial and harmful nutrients in relation to cardiometabolic diseases and mortality. Increasing attention in the scientific literature has been given to dairy foods, with controversies and confusion such as whether dairy (subtype) product intake should be consumed, whether they are related to cardiometabolic diseases and mortality, and whether they have a prominent role in healthy diets. The latest scientific evidence from large epidemiological prospective cohort studies confirmed neutral or beneficial associations between dairy foods and risk of cardiometabolic diseases and mortality. Interesting associations were found in Asian vs Western populations, but this has to be investigated further. The results should be placed in the context of observed heterogeneity, and potential residual confounding by healthy behaviours as well as the background diets. Future epidemiological studies should provide more details about dairy types and evidence from randomised controlled trials should be integrated with epidemiological studies to explore underlying mechanisms.

Keywords

Dairy foods; Cardiometabolic; Type 2 diabetes; Coronary heart disease; Stroke

Abbreviations

CHD 

coronary heart disease

SFA 

saturated fatty acids

RCT 

randomised controlled trial

Conflict of interest

SSSM received unrestricted grants for prior metaanalyses work by the Dutch Dairy Association, Global Dairy Platform, The Dairy Research Institute and Dairy Australia. She also received the Wiebe Visser International Dairy Nutrition Prize (2014) for her research output on dairy and cardiometabolic diseases. SSSM has received recent research funding (2019) to carry out epidemiological studies on dairy products and cardio-metabolic diseases from the Dutch Dairy Association and the Danish Dairy Research Foundation. JG reported no conflicts of interest.

1.1 Introduction

The number of people diagnosed with diabetes worldwide has more than doubled in the past 20 years and will continue to increase in the future. Globally there are 463 million people with diabetes, mostly type 2 diabetes (T2DM) in 2019, and this is projected to rise to 700 million by 2045 (Saeedi et al., 2019). One of the most worrying features of this rapid increase is the emergence of T2DM in young people, increase in undiagnosed diabetes, and highly prevalent prediabetes. Prediabetes is defined according to the diagnostic criteria published by the World Health Organisation in 2006, with fasting plasma glucose levels between 6.1 and 7.0 mmol/L, 2-h glucose levels between 7.8 and 11.0 mmol/L, and HbA1c levels between 6.0% and 6.5%. The number of people with prediabetes is expected to rise worldwide from 374 million in 2019 to 548 million in 2045 according to the International Diabetes Federation 9th edition (Saeedi et al., 2019). T2DM is a leading risk factor for the development of cardiovascular disease, which is the number one cause of death globally (WHO, n.d.). An estimated 17.9 million people died from cardiovascular diseases in 2016, representing 31% of all global deaths (WHO, n.d.). Of these deaths, 85% are due to heart attack and stroke. Dietary strategies to reduce the risk of developing cardiovascular disease include lowering of saturated fat intake. Milk and dairy foods are the major contributors of dietary saturated fats in Western diets. Healthy diet and lifestyle are often recommended as a strategy for risk reduction; 80%–90% of type 2 diabetes and cardiovascular disease can be prevented by adopting multiple healthy diet and lifestyle recommendations (Hu et al., 2001; Yang et al., 2012; Long et al., 2015; Lachman et al., 2016; Dong et al., 2018). In a recent study by the Global Burden of Disease Study investigators have revealed that dietary risks account for the greatest loss of global disability-adjusted life years (DALY) due to disease risk factors, overtaking smoking and hypertension (Lim et al., 2012; GBD 2017 Diet Collaborators, 2019). The loss of DALY are predominantly from T2DM and cardiovascular diseases, now often termed as cardiometabolic disease, and this presents a key challenge to nutrition scientists to identify effective dietary strategies and foods that can reduce disease risk and are acceptable and palatable to the population (Lovegrove and Givens, 2016). In this chapter, the latest scientific evidence from epidemiological studies on dairy foods in relation to cardiometabolic health will be described.

1.2 Types of dairy foods defined

Dairy is, according to the Cambridge English Dictionary, used to refer to foods that are made from milk, such as cream, butter, and cheese. In general, all mammalian milks (sheep, goat, camel, etc.) and their related products (cheese, sour cream, etc.) are classified as dairy. This may be confusing because dairy also refers to cattle and dairy farms according to the English Dictionary. Dairy foods are heterogeneous, containing solids, liquids, fermented and nonfermented foods; while milk, cheese, yoghurt are the main dairy products, they also include cream (sour cream) and ice cream, buttermilk, kefir, chocolate milk, butter, etc. Dairy foods contain many different types of products, with different textures and different tastes. The country where produced and feeding of the animals producing the milk and production processes further affect variety in dairy foods. Moreover, many foods contain dairy products, but are sold under different names, such as chocolate, custards, frozen desserts, and porridge. Within each dairy food, there are many variations ranging from high to low fat, with or without added sugars or fruits, to the type of fermentation. There are currently over 1800 different types of cheese, such as Brie, Gouda, Emmental, Roquefort, Camembert, Manchego, Cheddar, Feta, Gruyere, Monterey Jack, Stilton, and Grana Padano coming from different parts of the world. Epidemiological research of associations between dairy products and disease outcomes published prior to 2013 mostly considered dairy foods, combining heterogeneous dairy foods into one category as total dairy, and analyses of total high- and low-fat dairy intake. In various studies, different definitions of total dairy were used, including different combinations of dairy foods, which make comparisons between studies of associations between total dairy and cardiometabolic disease challenging. A shift was made over the past 5 years with more differentiation into different types of dairy foods, fermentation, and fat content, which enabled analyses of more specific associations between dairy subtypes and disease outcomes.

1.3 Dairy consumption in the world

Dairy foods are recommended in dietary guidelines of several countries (Table 1.1), generally advising milk, yoghurt, and cheese products at 2–3 servings per day. Dairy foods are increasingly consumed as indicated by the International Dairy Federation (Fig. 1.1 and Table 1.2). Dairy consumption is found to be highest in European countries, where most varieties of dairy foods are available on the market. From 2006 to 2013 there was globally a steep increase in per capita dairy product consumption (Fig. 1.1). Increases were limited in Europe (Centre National Interprofessionnel de l'Economie Laitière (CNIEL)/International Dairy Federation (IDF), Food and Agriculture Organization (FAO) of the United Nations, Population Reference Bureau (PRB), 2013). Dairy consumption, especially milk, is still low in many countries in particularly African and Asian countries (GBD 2017 Diet Collaborators, 2019) and projected to decline (Kearney, 2010) in many countries. Growth in the sales of dairy foods in Asia where people are generally lactose intolerant may not be biologically, culturally, or environmentally sound (Lee et al., 2015). The prevalence of lactose intolerance indeed varies from 100% in China and Japan to 50% in Mexico down to 15% in the United States white populations and 10% in Sweden (Bayless et al., 2017; Silanikove et al., 2015). The global average consumption of dairy foods is less than one serving per day (Lee et al., 2015). In South Asia, dairy consumption is highest in Pakistan. In North-East Asia, where lactase nonpersistence is most prevalent, the dairy consumption is highest in Japan, followed by Taiwan with intakes less than 1 serving per day. Interestingly, for liquid milk, the upper single dose of lactose tolerance seems to be about 25 g, which is the most that a single serve of dairy food might provide (Lee et al., 2015). In a historical perspective, several indicators were given for humans to overcome limitations imposed by lactose intolerance: (i) mutations, in which carriers of the lactose intolerance gene converted from being lactose intolerant to lactose tolerant; (ii) the ability to develop low-lactose products such as cheese and yoghurt, although not always widely consumed in Asian countries; and (iii) colon microbiome adaptation, which allows lactose-intolerant individuals to overcome its intolerance (Silanikove et al., 2015). Healthy eating guidelines in Asian countries include dairy foods (Table 1.1). Generally low to moderate dairy intake per day is well tolerated in most Asian populations and studies relating dairy intake to cardiometabolic diseases in these populations are rare (Lee et al., 2015).

Table 1.1

Fig. 1.1 Per capita Milk Consumption from 2006 to 2013. https://slideplayer.com/slide/11662620/ @copyrights permission granted CNIEL/IDF, FAO Food Outlook, PRB, n.d. Per Capita Milk Consumption From 2006 to 2012. Annual National Workshop for Dairy Economists and Policy Analysts presented in Boston in May.

Table 1.2

1.3.1 Nutrients context

Dairy foods such as milk, cheese and yoghurt are energy- and nutrient-dense products (Table 1.3). Dairy naturally contains various nutrients beneficial for health such as calcium, potassium, phosphorus, different vitamins such as B2, B12, and K2, and also nutrients less beneficial for health such as sodium, saturated fat, and added sugars. Vitamin D levels of dairy vary between countries depending on fortification. High- and low-fat products show comparable nutrient quantities in general. Compared to low-fat cheese, whole milk still contains considerably less fat per 100 g of product. There are small differences in saturated fat content between whole milk and skim milk (as g/100 g product) compared to high- and low-fat cheese. Cheese is relatively high in saturated fat and sodium content compared to the other dairy foods, and therefore not always included in healthy eating guidelines (Table 1.1).

Table 1.3

g, gram/100 gram product; mg, milligram/100 gram product; μg, microgram/100 gram product; En, energy; Carb, carbohydrates; SAFA, saturated fatty acids; PUFA, polyunsaturated fatty acids; Ca, calcium; P, phosphorus; K, potassium; Na, sodium.

a Whole milk 3.25% milkfat with added vitamin D (reference code = 01077).

b Milk reduced fat, 2% milkfat, with added vitamin A and D (reference code = 01079).

c Milk nonfat, skim, with added vitamin A and D.

d Cheese Mexican Blend (reference code = 01085).

e 01265 Cheddar Cheese, fat-free, nonfat (reference code = 01265).

f Yoghurt plain whole milk (reference code = 01116).

g Yoghurt plain skim milk (reference code = 01118).

https://ndb.nal.usda.gov/ndb/ (Accessed 4 December 2018).

There has been controversy in the literature as to whether dairy foods should have a prominent place in healthy diets, with alternating more or less focus on beneficial or potentially harmful nutrients (van Aerde et al., 2013; Tognon et al., 2018; Givens, 2010). Increasing attention in the scientific literature has been given to dairy foods because of controversies and confusion as to whether dairy (subtype) products should be consumed and whether or not these are associated with risk of cardiometabolic diseases and mortality.

1.4 Epidemiological studies

1.4.1 General principles

Epidemiology is the study of the distribution of diseases (e.g. T2DM, cardiovascular diseases, infections, allergies, etc.) in populations. Epidemiology is concerned with the frequency (counting disease, prevalence, and incidence) and pattern of health events (by time, place, and demographic characteristics) in a population. The purpose of epidemiological study is to understand what risk factors (aetiology) are associated with a specific disease, and how disease can be prevented in groups of individuals. Due to the observational nature of epidemiology, these studies cannot provide answers to what actually caused a disease, and further evidence on the cause-effect relationship from other types of studies (mechanistic studies, randomised controlled trials) need to be considered to make definite conclusions. Observational studies are an important category of epidemiological study designs. These can be categorised as: prospective cohort studies, retrospective cohort studies, case-cohort studies, (nested) case-control studies, and cross-sectional studies. Each study design has its own advantages and disadvantages. Prospective designs (cohort studies) are preferred for dairy and cardiometabolic diseases research and will be the main focus in this chapter. The main advantages of these prospective study designs are the ability to assess the exposure before the outcome occurs and confounding adjustments can be dealt with in statistical analyses. In an observational study, the investigator does not intervene (unlike in randomised controlled trials), rather simply observes and assesses the strength of the relationship between an exposure and outcome variable (Merril and Timmreck, 2006). The incidence of the outcome in the exposed group is directly compared to that of the unexposed group. A relative risk and confidence interval are calculated by dividing the incidence rates by the exposed vs. the unexposed group (adjusted for multiple confounders). If a relative risk is 1.0 then no association is found, if a relative risk is above 1.0 then a positive/higher risk association is found, and if a relative risk is below 1.0 then an inverse/lower risk association is found. A relative risk always has to be interpreted taking into account the confidence interval around the estimate. A wide confidence interval indicates lack of power and unreliable estimates. Residual confounding remains an issue in this type of research, because intake of many dairy foods is known to be related to other healthy or unhealthy behaviours, not always accounted for in adjustment models.

Dietary intake data are mostly self-reported data using extensive food frequency questionnaires, dietary history methods, 24-h recall methods, or food diaries. It is difficult to estimate exact intake amounts of dairy foods with these methods, but these methods are suitable to rank people in different categories of intake and to compare consumption extremes related to risks of cardiometabolic diseases.

1.4.2 Dose-response metaanalyses techniques

Traditionally, metaanalyses were performed pooling risk estimates from prospective cohort studies for high vs low dairy product intake. The meaning of a pooled risk estimate was not clear, because this was not directly linked to a particular dosage of dairy foods, and high and low dairy consumption varied between studies. Interpretations about the dosage/quantity were impossible to derive from underlying studies because each study used a different questionnaire for food intake, ranking study participants into high and low intake based on a different underlying range of intake for each study. A more sophisticated method, dose-response metaanalysis, includes intake/dose generally expressed in the same unit across studies (e.g. in grams per day) and allows investigation of linear or nonlinear associations. The key to this approach is to first calculate the study specific slopes and then pool results across studies. Assumptions have to be made on how to deal with the lower and upper limits of various dairy intake categories used in the analysis (i.e. tertiles, quartiles, quintiles of dairy intake) and how to obtain grams per day food intake from frequency data (times per week using standard portion sizes or country-specific portion sizes). Choices have to be made as to which result is to be extracted from each article. For example, if studies presented several statistical models, the model that included most confounders is usually chosen. Linearity of associations is investigated using spline analysis and dose-response metaregression (Generalised least-square trend; GLST). Splined variables have to be created in order to select the most appropriate knot points of nonlinear associations based on goodness-of-fit tests and Chi-square statistics. The shape of the associations within individual studies are visualised by means of Ding's spaghetti plots (Soedamah-Muthu et al., 2012; Gijsbers et al., 2016; de Goede et al., 2016; Guo et al., 2017). Dose-response metaanalyses offer more insight on the direct association between for example dairy foods and risk of cardiometabolic disease, taking into account the shape of the association (Gijsbers et al., 2016; de Goede et al., 2016; Guo et al., 2017). Large heterogeneity indicates between-study variation and needs to be explored further by metaregression and subgroup analyses. Generally, subgroup analyses by continent, age groups, sex, study outcome types, follow-up duration, confounder adjustments (optimal confounder adjustments vs. limited confounder adjustments) are carried out. Results always have to be interpreted in the light of observed heterogeneity.

1.5 Current state of evidence on dairy foods and cardiometabolic diseases

1.5.1 Prospective studies on dairy foods and type 2 diabetes

There is an overwhelming amount of evidence on the association between dairy foods and T2DM from prospective cohort studies, summarised in several metaanalyses (Gijsbers et al., 2016; Soedamah-Muthu and De Goede, 2018; Yu and Hu, 2018; Drouin-Chartier et al., 2016a; Aune et al., 2013; Gao et al., 2013; Tong et al., 2011; Elwood et al., 2008; Chen et al., 2014; Alvarez-Bueno et al., 2019). The results from all metaanalyses showed consistently neutral or inverse associations for intake of total and low-fat dairy foods, with the most striking inverse association between yoghurt intake and T2DM. A very recent pooling of three large USA cohort studies (two Nurses Health Studies and Health Professionals Follow-up Study) confirmed these results with longitudinal exposure data and showed that increasing intake of yoghurt was associated with a moderately lower risk of T2DM (Drouin-Chartier et al., 2019). They also showed opposite results for cheese, with increasing cheese consumption associated with a moderately higher risk of T2DM (Drouin-Chartier et al., 2019). A potential explanation for the discrepancy of this study with existing metaanalyses given by the authors is the way cheese is most often consumed in the USA as an ingredient in mixed dishes (for example pizza, hamburgers, sandwiches) and high in refined carbohydrates. The studies by Soedamah-Muthu and De Goede (2018) and Gijsbers et al. (2016) are the most complete with a total of 26 prospective cohort studies. Total dairy intake (per 200 g/day) was borderline significantly associated with a 3% lower risk of T2DM, and low-fat dairy intake was also borderline significantly associated with a 4% lower risk of T2DM (I² = 60%) (Soedamah-Muthu and De Goede, 2018). Yoghurt intake had the most striking result, with a nonlinear inverse significant association with T2DM (relative risk (RR) = 0.86, 95% confidence interval (CI): 0.83–0.90, P < .001, I² = 69%, at 80 g/day compared with 0 g/day) (Fig. 1.2, Ding's spaghetti plot of yoghurt intake and risk of T2DM).

Fig. 1.2 Ding's Spaghetti plot for the association between yoghurt consumption and risk of type 2 diabetes, summarising data from 13 prospective cohort studies (14 samples).

In all these metaanalyses considerable heterogeneity (60%–69%) was present, which could not be explained by metaregression and subgroup analyses (Soedamah-Muthu and De Goede, 2018). Metaanalyses of high-fat dairy, fermented dairy, cheese, and milk intake showed no significant associations with incident T2DM. The differences in associations with T2DM risk for high-fat (null association) compared to low-fat dairy (moderately inverse) intake was also shown in previously published metaanalyses (Drouin-Chartier et al., 2016a). Subgroup analyses of the associations between total dairy intake and T2DM risk by Gijsbers et al. (2016) suggested a nonsignificant inverse association in Asian populations (three studies, RR: 0.85 per 200 g/day; 95% CI: 0.65, 1.12), but no association was observed for European populations (six studies). Only a limited number of studies from Asia (n = 3) were available for these analyses, and these country-specific associations should be further investigated in the future. Butter is nutritionally distinct from other dairy foods and generally not included in analyses of dairy products and type 2 diabetes, but a separate metaanalysis was published. In this metaanalysis by Pimpin et al. (2016) summarised data from four cohorts and found that butter consumption was associated with a lower incidence of T2DM, with a 4% lower risk per daily 14 g (1 tablespoon) serving (RR = 0.96, 95% CI: 0.93–0.99, P = .21), moderate heterogeneity was seen (I² = 42%). The authors of this study have acknowledged that these were small overall associations, which do not support a need for major emphasis in dietary guidelines on either increasing or decreasing butter consumption, and recommended further research on health effects of butter and dairy fat (Pimpin et al., 2016). All the evidence of the association between yoghurt and butter intake and the risk of T2DM have been derived from observational epidemiological studies, with moderate to large heterogeneity and residual confounding remaining an issue. There is evidence that yoghurt intake is related to healthy behaviours (Tremblay and Panahi, 2017) and although confounder models in all studies included in the metaanalyses adjusted for healthy behaviours, there could still remain residual confounding. The impact of dairy foods on T2DM cannot be fully dissociated from that of the foods it replaces (Tremblay and Panahi, 2017; Lamarche et al., 2016). The background diet and habits are generally not captured in epidemiological studies and is an interesting area for future research.

1.5.2 Prospective studies on dairy foods and coronary heart disease

There is good evidence from prospective cohort studies that investigated the association between dairy intake or specific types of dairy product and risk of coronary heart disease (CHD) (Guo et al., 2017; Soedamah-Muthu and De Goede, 2018; Drouin-Chartier et al., 2016a; Mullie et al., 2016; Chen et al., 2017; Bechthold et al., 2017; Gille et al., 2018; Alexander et al., 2016a; Qin et al., 2015; Soedamah-Muthu et al., 2011; Fontecha et al., 2019). The results from all metaanalyses showed that, based on moderate- to high-quality evidence, total dairy, full-fat dairy, low-fat dairy, milk, cheese, and yoghurt consumption has no association with the risk of CHD. In line with this, the PURE cohort investigators published international data from 21 countries in five continents on total dairy foods intake in relation to risk of myocardial infarction and found no evidence for an association (Dehghan et al., 2018). On the contrary, in 2017, Gille et al. (2018) concluded that there was moderate evidence for an inverse association between CHD risk and the consumption of cheese based on three metaanalyses (Chen et al., 2017; Qin et al., 2015; Alexander et al., 2016b), but this is a selection of the evidence. Butter is nutritionally distinct from other dairy foods and generally not included in analyses of dairy products and coronary heart disease, but a separate metaanalysis was published. The metaanalysis by Pimpin et al. (2016) found that butter intake (per 14 g/day) was not significantly associated with CHD risk (RR = 0.99, 95% CI: 0.96–1.03; P = .54).

1.5.3 Prospective studies on dairy foods and stroke

There are many metaanalyses of prospective cohort studies which have investigated data on dairy intake or specific types of dairy product and incident stroke (de Goede et al., 2016; Mullie et al., 2016; Soedamah-Muthu and De Goede, 2018; Yu and Hu, 2018; Drouin-Chartier et al., 2016a; Chen et al., 2017; Soedamah-Muthu et al., 2011; Alexander et al., 2016b; Fontecha et al., 2019).

In 2016, we pooled 18 prospective cohort studies from 11 countries with 8–26 years of follow-up that included 762,414 individuals and almost 30,000 stroke events based on a search up to October 2015 (de Goede et al., 2016). An increment of 200 g of daily milk intake was associated with a 7% lower risk of stroke (RR = 0.93: 95% CI: 0.88–0.98; P = .004; I² = 86%). RRs were 0.82 (95% CI: 0.75–0.90) in East Asian (n = 4 studies, 5 samples) and 0.98 (95% CI: 0.95–1.01) in Western countries (n = 3 studies, 4 samples) (median intakes 38 and 266 g/day, respectively) with less, but still considerable, heterogeneity within the continents. Nonsignificant inverse associations between semiskimmed milk intake and stroke were found (four Western studies, median intake: 150 g/day): 0.96 (95% CI: 0.90–1.03) per 200 g/day with heterogeneity (I² = 68%, P = .01), whereas the association with full-fat milk showed a higher risk of stroke. Based on a limited number of studies, full-fat milk (n = 4 studies, RR of 1.04 (95% CI: 1.02–1.06) per 200 g/day) was positively associated with stroke risk, whereas full-fat total dairy (n = 6) as well as low-fat dairy (n = 7) intake were inversely associated (de Goede et al., 2016; Soedamah-Muthu and De Goede, 2018). Differences in associations between full-fat (null association) and low-fat dairy (weak inverse association) products and stroke were found in prior metaanalyses (Drouin-Chartier et al., 2016a). Cheese intake was marginally inversely associated with stroke risk (RR = 0.97; 95% CI: 0.94–1.01 per 40 g/day). The strongest inverse association with incident stroke was found around 125 g/day for milk intake and around 25 g/day for cheese. No associations were found for yoghurt, butter, or total dairy intake. Butter is nutritionally distinct from other dairy foods and generally not included in analyses of dairy products and stroke, but a separate metaanalysis was published. The metaanalysis by Pimpin et al. found that butter intake was not associated with stroke risk (RR = 1.01; 95% CI: 0.98–1.03, P = .74 per 14 g (1 tablespoon)/day) (Pimpin et al., 2016). Analyses for total dairy and milk were updated with four new cohort studies by Soedamah-Muthu and de Goede, who confirmed similar results, an incre?ment of 200 g/day milk intake was associated with an 8% lower risk of stroke, RRmilk and stroke = 0.92, 95% CI: 0.88–0.97, I² = 85% (Soedamah-Muthu and De Goede, 2018). RRs were 0.82 (95% CI: 0.75–0.89) in East Asian and 0.98 (95% CI: 0.95–1.01) in Western countries (median intakes of 38 and 266 g/day, respectively) (Fig. 1.3). In the large PURE cohort study including data from 21 countries from five continents, dairy consumption was found to be associated with a lower risk of stroke, RR = 0.66, 95% CI: 0.53–0.82, P = .0003 (Dehghan et al., 2018). It was not clear whether this association was due to milk or cheese intake. All evidence of associations between milk and cheese intake and the risk of stroke has been derived from observational epidemiological studies; large unexplained heterogeneity and residual confounding remain an issue in these studies. As noted earlier, the background diet is not generally captured in epidemiological studies, and therefore, hypothetically, the association of a higher milk intake with a lower risk of stroke could potentially be due to, for example, a lower intake of sugar-sweetened

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