bmj...confidential: for review only 1 the who draft guidelines on dietary saturated and trans-fatty...

Confidential: For Review OnlyThe WHO draft guidelines on dietary saturated and trans-

fatty acids: time for a new approach?

Journal: BMJ

Manuscript ID BMJ-2019-049402

Article Type: Analysis

BMJ Journal: BMJ

Date Submitted by the Author: 22-Feb-2019

Complete List of Authors: Astrup, Arne; Copenhagen University, Dept of Nutrition, Exercise and SportsBertram, Hanne; Aarhus Universitet, Food ScienceBonjour, Jean-Philippe; Hopitaux Universitaires de Genevede Groot, Lisette; Wageningen University, de Oliveira Otto, Marcia; University of Texas Health Science Center at Houston, Department of EpidemiologyFeeney, Emma; University College Dublin, Institute of Food and HealthGarg, Manohar L.; Univ NewcastleGivens, D. I.; Univ ReadingKok, Frans; Wageningen University, Division of Human NutritionKrauss, Ronald; Children's Hospital Oakland Research InstituteLamarche, Benoît; Universite Laval Faculte de medecine, NutritionLecerf, Jean-Michel; Institut Pasteur de Lille, Nutrition & Activité PhysiqueLegrande, Philippe; Agrocampus-INRAMcKinley, Michelle; Queen's University Belfast, Centre for Public Health, School of MedicineMicha, Renata; Tufts University, Friedman School of Nutrition Science and PolicyMichalski, Marie-Caroline; Universite Claude Bernard Lyon 1, INRA, INSERM, CarMen LaboratoryMozaffarian, Dariush; Friedman School of Nutrition Science and Policy, Tufts University, Soedamah-Muthu, Sabita; Wageningen Universiteit, Division of Human Nutrition

Keywords: saturated fatty acids, dietary guidelines

https://mc.manuscriptcentral.com/bmj

BMJ

Confidential: For Review Only

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The WHO draft guidelines on dietary saturated and trans-fatty acids: time for a new approach?

Standfirst: The 2018 WHO draft guidelines on fatty acids fail to consider the importance of the food matrix argue Arne Astrup and colleagues.

Arne Astrup, Hanne C.S. Bertram, Jean-Philippe Bonjour, Lisette C.P.G.M. de Groot, Marcia C. de Oliveira Otto, Emma L. Feeney, Manohar Garg, Ian Givens, Frans J. Kok, Ronald M. Krauss, Benoît Lamarche, Jean-Michel Lecerf, Philippe Legrand, Michelle McKinley, Renata Micha, Marie-Caroline Michalski, Dariush Mozaffarian, Sabita S. Soedamah-Muthu

Arne Astrup, Head of Department, Nutrition, Exercise and Sport, University of Copenhagen, DK-2200 Copenhagen N, Denmark, [email protected]. Hanne CS Bertram, Professor, Department of Food Science, Aarhus University, Denmark, [email protected]. Jean-Philippe Bonjour, Honorary Professor of Medicine, Geneva University Hospitals & Faculty of Medicine, Switzerland, [email protected]. Lisette CPGM de Groot, Professor, Division of Human Nutrition, Department of Agrotechnology and Food Sciences, Wageningen University, The Netherlands, [email protected]. Marcia C. de Oliveira Otto, Assistant Professor, University of Texas, Houston, USA, [email protected]. Emma L. Feeney, Assistant Professor, Institute of Food and Health, University College Dublin, Republic of Ireland, [email protected]. Manohar Garg, Director, Nutraceutricals Research Program, University of Newcastle, Callaghan NSW 2308, Australia, [email protected]. Ian Givens, Professor, Director, Institute for Food, Nutrition and Health, University of Reading, UK, [email protected]. Frans J. Kok, Emeritus Professor Nutrition and Health, Wageningen University, Netherlands, [email protected]. Ronald M. Krauss, Senior Scientist and Dolores Jordan Endowed Chair, Children's Hospital Oakland Research Institute & UCSF Benioff Children's Hospital Oakland, USA, [email protected]. Benoît Lamarche, Chair of Nutrition, Institute of Nutrition and Functional Foods, Université Laval, Québec, Canada, [email protected]. Jean-Michel Lecerf, Chef du Service de Nutrition & Activité Physique, Institut Pasteur de Lille, France, [email protected]. Philippe Legrand, Professor, Agrocampus-INRA, Rennes, France, [email protected]. Michelle McKinley, Reader, Institute for Global Food Security, Queen's University Belfast, UK, [email protected]. Renata Micha, Associate Professor, Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA, USA, [email protected]. Marie-Caroline Michalski, Research Director, INRA, INSERM, Univ Lyon, Université Claude Bernard Lyon 1, CarMeN laboratory, CRNH Rhône-Alpes, Oullins, France, [email protected]. Dariush Mozaffarian, Dean, Friedman School of Nutrition Science & Policy, Tufts University, Boston, USA, [email protected]. Sabita S. Soedamah-Muthu, Associate Professor, Medical and Clinical Psychology, Tilburg University, Netherlands, [email protected]

Correspondence to: Professor Arne AstrupHead of Department of Nutrition, Exercise and Sports, University of CopenhagenNørre Alle 51, DK-2200 Copenhagen N, Denmark Email: [email protected] Tel.: +45 3533 2476

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Key Messages

The 2018 WHO draft guidelines on dietary saturated fatty acids (SFA) and trans-fatty

acids recommend reducing total SFA intake and replacing them with poly- and

monounsaturated fatty acids.

The recommendations fail to take into account considerable evidence that the health

effects of SFA vary depending on the specific fatty acid, and further depend on the

specific food source.

Maintaining general advice to reduce total SFA will work against the intentions of the

guidelines, and weaken their impact on chronic disease incidence and mortality.

A food-based translation of the recommendations for SFA intake would avoid

unnecessary reduction or exclusion of foods that are key sources of important

nutrients.

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Introduction

Non-communicable diseases are the world’s leading cause of death, responsible for 72% of the

54.7 million deaths in 2016 (1). Cardiovascular diseases (CVD) are responsible for approximately

45% of all deaths from non-communicable diseases with modifiable risk factors such as diet,

physical activity, smoking, and alcohol intake, being major causes of CVD.

Among dietary factors, the World Health Organisation (WHO) considers saturated fatty acids (SFA)

and trans-fatty acids (TFA) to be of particular importance. Consensus exists on health benefits of

eliminating industrially produced TFA (2). Foods containing more than 2% total fat as TFA were

banned in Denmark in 2004 and similar legislation is soon to be implemented throughout the

European Union. In the United States the Food and Drug Administration no longer classifies

industrial trans-fats as “generally regarded as safe”.

WHO dietary guidelines are regarded by many governments as state-of-the–art scientific evidence,

and are translated into regional and national dietary recommendations. These guidelines have

potential health implications for billions of people, and both the consistency of the science behind

such recommendations and validity of the conclusions are crucial.

WHO draft guidelines

WHO draft guidelines on dietary SFA and TFA for adults and children were published for

consultation in May 2018, recommending reduced intake of total SFA and replacement with

polyunsaturated fat and monounsaturated fat to reduce CVD incidence and mortality (2).

Unfortunately, the recommendation fails to take into account considerable evidence that the

health effects of SFA are different for different types of fatty acid and that the composition of the

food in which SFAs found are crucially important (3-5) (Box 1). Food composition has a substantial

impact on lipid digestion, absorption kinetics, and postprandial lipemia (6), which is an

independent CVD risk factor (7).

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Box 1. SFA in food products

SFA are found in a wide diversity of foods that vary in composition and structure resulting in

completely different physiological effects. For example, dairy products have very different

compositions and milkfat structures. Full-fat milk is a natural emulsion of fat globules, initially

covered by their biological milk fat globule membrane (MFGM), while in marketed homogenized

milk, droplets are much smaller and covered with proteins. In turn, butter is a water-in-oil

emulsion. Yogurt is a fermented food containing live cultures, in which milk fat globules are

dispersed in the gelled milk protein matrix. Cheese is one of the most complex dairy matrices. It

is a fermented food containing live cultures, where fat is present within milk fat globules, and

sometimes free fat inclusions, in a more or less solid matrix rich in milk proteins, calcium and

MFGM. Ice cream contains a combination of crystallized fat globules around air bubbles, and ice

crystals in a liquid syrup phase.

SFA containing foods from other animal sources also have a wide range of compositions and

structures. Animal fats, such as lard and tallow, are 100% lipids. In unprocessed meat, lipids are

mostly present within adipocytes and intracellular lipid droplets of muscle. Processed meats can

contain fat inclusions in a gelled protein matrix, free fat domains, and remnant adipocytes,

according to processing. Egg yolk contains lipids structured as lipoproteins of both low- and

high-density.

In processed foods such as pastries and cookies, the fat inclusions (composed of palm oil, butter

etc.) are embedded within a more or less solid, often sugar-rich, carbohydrate matrix. Chocolate

is composed of particles (e.g. sugar), and fermentation products from cocoa bean embedded in

solid fat. SFA-rich vegetable oils such as palm oil and coconut oil are 100% lipids.

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The SFA in these different food matrices are also present as different types of lipid molecules -

notably triglycerides and phospholipids. In these molecules SFA can be esterified at different

positions depending on fat/oil source.

*Adapted from the review Michalski et al. (6)

How robust is the evidence linking saturated fat to cardiovascular disease?

Evidence from randomized controlled trials with clinical end-points

Several recently published meta-analyses of observational studies and RCTs do not show that total

SFA are harmful (8-10). In contrast, a Cochrane analysis that only included data from 15 RCTs

found an association between reducing SFA intake and “combined cardiovascular events” (a

composite end-point) [RR 0.83 (0.72 to 0.96)]. However, the study showed no significant

association between reducing SFA and total mortality, CVD mortality, myocardial infarction, non-

fatal myocardial infarction, stroke, coronary heart disease (CHD) events, and CHD mortality (11).

Evidence from randomized controlled trials with surrogate end-points

The WHO draft guidance relies heavily on a meta-analysis of 84 RCTs that tested the effect of

modifying SFA intake on serum lipid and lipoprotein levels (12). Focusing on total SFA, ignoring

food sources, and using surrogate end-points is problematic for a number of reasons.

First, it is important to recognise that not all SFAs are equal and focusing on total SFAs is

problematic because the magnitudes and even directions of the effects on both surrogate end-

points and long-term end-points vary depending on the SFA being studied. For example, using the

ratio of total cholesterol to HDL cholesterol as biomarker of CVD risk, the SFA lauric acid (12:0)

increases the ratio, whereas the other SFA’s myristic acid (14:0) and palmitic acid (16:0) have little

effect on the ratio, and stearic acid (18:0) reduces the ratio slightly (13). Moreover, high plasma

levels of the SFA heptadecanoic acid (17:0), which reflects a high intake of this SFA, is associated

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with a reduced risk of CHD (14). These observations show that SFA’s cannot we viewed as one

homogeneous group with regard to effects of diet on disease risk.

Second, it is unclear if the observed changes in serum lipoproteins translate into a reduction in

cardiovascular end-points and mortality regardless of food source (3). The majority of trials

included in the meta-analysis did not investigate whole food sources of SFA, but instead compared

the effect of diets supplemented with fats rich in SFA, mono- or polyunsaturated fat, e.g. cocoa

butter, olive oil, soybean oil, dairy butter, while other studies used synthetic fats, e.g.

high in myristic acid (12). The food matrix in which the fatty acids exist may be more important for

the effect on CVD risk than the SFA content (Box 1).

Third, the meta-analysis that the draft WHO guidance rests on used mainly LDL-cholesterol

concentration as a marker for CVD risk. This strategy may lead to misleading conclusions because

using LDL-cholesterol concentration as a marker of diet effects on CVD risk has limitations.

Atherogenecity of LDL-particles is determined by resistance against oxidation, size, density,

composition, cytotoxicity, and presence or absence of other lipoproteins such as apolipoprotein

CIII. LDL-particle size is an important determinant of CVD risk, and small and medium-sized LDL

particles show the strongest association with cardiovascular events, whereas large LDL-particles

are not associated with CVD risk (15). There is evidence that the increase in LDL-cholesterol from

total SFA consumption is associated with a parallel increase in LDL-particle size, which means that

an increase in LDL-cholesterol caused by increased intake of SFA does not necessarily translate

into an increased CVD risk (16).

The PURE study, which included over 100,000 people, illustrates why a broader view biomarkers of

CVD is needed to inform guidelines. The study found that diets that were high in SFAs are

associated with higher LDL-cholesterol, but also with higher HDL and lower triglycerides, and

lower ApoB/ApoA ratio (17), but not with CVD events apart from a lower risk of stroke (18).

ApoB/ApoA ratio is a strong risk marker of CHD and stroke, and is a marker of the small, dense

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artherogenic LDL-particles, and provides more risk information than LDL-cholesterol alone. In the

PURE study diets high in SFA were associated with lower (i.e. protective) ApoB/ApoA ratio, while

carbohydrates were associated with higher ratios (17). The relevance of this observation is

confirmed by at least three randomized trials comparing diets with different fats on hard end-

points (10,19,20). A significant reduction in major CVD events without any reduction in LDL-

cholesterol was produced by Mediterranean-style diets in the Lyon Diet Heart Study (19) and in

the PREDIMED trial (20), which both showed that LDL-cholesterol concentration is not a valid

biomarker for alterations in CVD risk caused by dietary changes. A re-analysis of the Minnesota

Coronary Experiment, a double blind randomized controlled trial that tested whether replacement

of SFA with polyunsaturated fat reduces coronary heart disease and death, supports that serum

cholesterol is not a valid surrogate biomarker to assess CVD risk when making changes in SFA

intake (10). Despite the finding that the polyunsaturated fat diet produced a 13% greater

reduction in serum cholesterol than the SFA diet, there was no reduction in CVD end-points (20).

By contrast, the authors found a 22% higher mortality for each 0.78 mmol/L reduction in serum

cholesterol caused by the polyunsaturated diet (10). The same authors also conducted a

systematic review and a meta-analyses, and found that cholesterol lowering interventions using

polyunsaturated fat diets did not show any evidence of benefit on mortality from coronary heart

disease (1.13, 0.83 to 1.54) or all cause mortality (1.07, 0.90 to 1.27) (10).

In conclusion, guidelines that rely on a pooled effect on LDL-cholesterol of total SFA from all food

sources to predict changes in CVD risk cannot be considered evidence-based.

Evidence from observational studies and food-based analyses of cardiovascular disease risks

The WHO draft guidelines exclude substantial evidence derived from observational studies and

meta-analyses of prospective cohort studies. The guideline argues that the quality of evidence for

relevant outcomes is lower than in analyses of RCTs, and that it was not possible to assess

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potential differential effects of replacing SFA with different nutrients (8,9,21). However,

observational studies are valuable for assessing the association of SFA with long term end-points,

such as CVD.

Observational studies are also particularly useful for analyses that focus on the foods consumed in

people’s diet rather than simply focusing on individual nutrients. It has long been recognised that

evidence suggests the food matrix is more important than its fatty acid content for predicting the

effect of a food on CHD risk. This was the conclusion of an expert consensus panel, that some of us

took part in, now nearly 10 years ago (21).

Evidence linking foods high in saturated fat to cardiovascular disease

Today, there are ample food-based studies that have examined whether foods with high contents

of SFA contribute to CVD events and mortality. To illustrate where the science stands we have

briefly reviewed the evidence for the most popular foods high in SFA.

Eggs

Eggs contain ~2.6 g SFA/100 g, and can be a significant contributor to SFA intake, and limiting egg

consumption has been recommended to reduce intake of saturated fat and cholesterol. However,

eggs are also nutrient-dense, providing important nutrients that are not widely available in other

foods. Meta-analyses of prospective, observational studies have not found higher egg

consumption to be associated with risk of CHD, but with lower risk of stroke; subgroup analyses

found higher CHD risk in diabetic populations (22,23). By contrast, RCTs have found neutral or

beneficial effects on markers of diabetes and CVD (24).

Dark chocolate

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Dark chocolate also contains substantial amounts of SFA, but mainly stearic acid. Other

components in dark chocolate may be more important than SFA content for risk of CVD and type 2

diabetes. Experimental and observational studies suggest that dark chocolate intake may

contribute to prevention of CVD and diabetes (25-28). The WHO draft guidelines state that stearic

acid has no harmful effect on ’any outcome assessed’, yet do not translate this into food-based

recommendations.

Butter

Butter is a particularly SFA-dense food. Yet, in a recent meta-analysis of prospective observational

studies with median butter consumption ranging from 4.5 to 46 g/d, butter consumption was

weakly associated with all-cause mortality per 14g/day (RR = 1.01, 95%CI = 1.00, 1.03); was not

associated with CVD, CHD, or stroke; and was inversely associated with incidence of diabetes. (29).

Yogurt and cheese

Dairy products are the major source of SFA and the main targets of the WHO to reduce intake of

SFA. However, dairy is also a major source of protein, calcium, and other nutrients. However,

food-based meta-analyses consistently find no association between dairy foods and increased risk

of CVD. Recently, the large scale PURE-study reported dairy consumption to be associated with

lower risk of mortality and major cardiovascular disease events in a diverse multinational cohort

(30). Indeed, both mechanistic research and observational studies find that whole-fat fermented

dairy, e.g. cheese and yogurts, may actually reduce CVD and diabetes risk (30-33). Moreover, a

pooled individual-level analysis of nearly 65,000 participants across international cohorts found

that circulating and tissue biomarker concentrations of odd-chain SFA (15:0, 17:0) and natural

ruminant TFA (trans-16:1n7), that at least partly reflect dairy fat consumption, are associated with

significantly lower incidence of diabetes (34).

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Recent meta-analyses have found that cheese and yogurt intakes are inversely associated with

CVD risk (35), and that a high intake of cheese is associated with an 8% lower risk of CHD, and a

13% lower risk of stroke (35,36). Whole-fat dairy may play a particular role in the prevention of

type 2 diabetes, a known risk factor for CVD (31,37).

Cheeses and yogurts consist of complex food matrices and ingredients that include different fatty

acids, proteins (whey and casein), minerals (calcium, magnesium, phosphate), sodium, and

phospholipid components of milk fat globule membrane (MFGM) (10) (Box 1). Cheese has a high

fat content, but is more similar in composition to yogurt and milk than to butter, due to protein,

mineral, and MFGM contents (10,38). Yogurt and cheese are also fermented dairy products

containing bacteria and bacterially-produced bioactive peptides, short chain fatty acids, and

vitamins such as menoquinones (vitamin K2).

Meat

The current evidence suggests major differences in associations of unprocessed red meat vs.

processed meat intake with CVD, independent of SFA contents. A meta-analysis found that intake

of processed meat, but not red meat, was associated with a higher risk of CHD (39). Another meta-

analysis found no difference in CVD risk factors between groups with more vs. less than 0.5 daily

servings of meat (40). Prospective cohorts also suggest stronger associations of processed meat

consumption, compared to unprocessed red meat consumption, in relation to type 2 diabetes.

(40,41). Meat is a major source of protein, bioavailable iron, minerals and vitamins. In modest

amounts (up to 1-2 servings/week), unprocessed red meat constitutes an important part of the

diet for the elderly and low-income populations in numerous developing countries (42,43).

Discussion

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WHO recommendations to reduce total SFA to prevent CVD have no basis in the existing evidence

related to any of the major food sources, including dairy foods, unprocessed red meats, or even

processed meats.

The mechanisms by which diets and dietary fats can influence CVD events and death are complex

and not mediated by changes in concentrations in total and LDL-cholesterol. Indeed, diets that

have been shown to reduce CVD event and mortality may actually increase LDL-cholesterol. So

while LDL-cholesterol is a valid marker to monitor efficacy of statins in the management of

hypercholesterolemia, it should not be used to assess cardio-protective effects of diets, neither as

scientific risk assessment for the definition of dietary guidelines, nor for the individual. There is

clearly a need to develop risk assessment algorithms using other biomarkers such as triglycerides,

LDL-particle size etc.

It is important to bear in mind the historical evolution of guidelines, if we are to understand why

the current misconceptions about SFA seem to be so solidly anchored in the major public health

bodies, including the WHO. Up until the 1950-ties nutrition science focused on single nutrient, and

major public health policies addressed deficiencies in micronutrients, leading to fortification of

selected staple foods, e.g. iodine in salt, vitamin B3 and iron in wheat flour and bread (3). Nutrition

science then changed focus to policies to prevent chronic diseases such as CVD in affluent

countries, and the single nutrient approach was maintained. Based mainly on less robust cross-

country comparisons between intakes of SFA and CVD mortality, the simple two-step deductive

reasoning that “dietary fat, and SFA in particular, increases serum cholesterol” and “serum

cholesterol is a risk factor for CHD” led to the conclusion that all dietary fat, and SFA in particular,

should be reduced in order to reduce the incidence of CVD (3). The US dietary guidelines 1980,and

international guidelines ever since, have focused on reducing SFA.

The guidelines not only have immense impact on dietary advice for individuals, but also on

production of foods, ready to eat meals, and meals at restaurants. Historically, the focus to reduce

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SFA led to proliferation of industrially produced food products low in fat, saturated fat, and

cholesterol, and dissemination of products based on technologies to replace SFA ,e.g. by

margarine and spreads based on partial hydrogenation of vegetable oils that increased the

content of trans fatty acids to up to 40% of total fat (44). The widespread consumption of trans fat

is considered to have been responsible for 6 to 19% of all CHD events (45), and to cause about 11

000 heart attacks and 7000 avoidable deaths in the UK every year (46). Denmark banned trans fat

in 2004 and has subsequently seen the largest decline in CHD mortality in EU, and analyses have

attributed this development to the elimination of trans fat from foods (47). The example of how

soft science on SFA led to policies that have essentially killed millions of people globally should be

a lesson learnt, yet the food industry still follows WHO guidelines and seeks ways to replace SFA in

foods products with alternatives, and there is a high risk that these solutions may well have

adverse effects on health.

We believe that recommendations to reduce intake of total SFA without considering specific fatty

acids and food sources are not evidence-based and will distract from other more effective food-

based recommendations. There is a risk that such recommendations may actually cause a

reduction in the intake of nutrient-dense foods that that are important for preventing disease and

improving health. We’re concerned that, based on several decades of experience, a focus on total

SFA may have the unintended consequence of misleading governments, consumers, and industry

toward promoting foods low in SFA but rich in refined starch and sugar.

The WHO SFA guidelines should consider different types of fatty acids and, more importantly, the

diversity of foods containing SFA that may be harmful, neutral, or even beneficial in relation to

major health outcomes. We strongly recommend a more food-based translation of how to achieve

a healthful diet and reconsideration of the draft guidelines on reduction in total SFA.

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Contributors and sources

This is a summary of an international collaboration in response to the WHO hearing, May 2018. All

the authors contributed equally, each addressing specific questions within their core areas of

expertise. Arne Astrup is guarantor of the article. Astrup is expert in dietary prevention of obesity,

type 2 diabetes and CVD, and chaired the Danish Nutrition Council that produced the scientific

reports that lead Denmark to ban industrial trans-fat in foods in 2014, the first country in the

world to do so.

Conflicts of Interest

AA: has received financial support from Danish Dairy Foundation, Global Dairy Platform, Arla

Foods Amba, Denmark & European Milk Foundation for projects, conducted at the University of

Copenhagen exploring the effects of dairy fats and cheese consumption on human health. The

European Milk Foundation sponsored the Expert Symposium on the Dairy Matrix 2016, organised

by AA, and co-chaired by AA and IG. AA has received travel expenses and honoraria in connection

with meetings and lectures from Danone, Arla Foods, Swedish Milk Foundation, and Global Dairy

Platform. HCSB: through employment at Aarhus University, has received financial support for

research activities from Arla Foods amba, the Danish Dairy Research Foundation, and Arla Food for

Health (a consortium between Arla Foods amba, Arla Foods Ingredients Group P/S, Aarhus

University and University of Copenhagen). J-PB: None. LCPGMdeG: None. MCdOO: None. ELF: has

received research funding from Food for Health Ireland, a dairy technology center part-financed

by Enterprise Ireland and partly by dairy companies in Ireland. ELF has received speaking expenses

from the National Dairy Council and the European Milk Forum. MG: None. IG: Estonian

BioCompetance Centre of Healthy Dairy Products, Consultant to the Dairy Council on fats in dairy

products and cardiometabolic disease; have received travel expenses and honoraria in connection

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with meetings and lectures from the Dairy Council, Dutch Dairy Association, Global Dairy Platform

and the International Dairy Federation. FJK: None. RMK: Grant funding from Almond Board of

California and Dairy Management, Inc. BL: Chair of Nutrition at Laval University, which is

supported by private endowments from Pfizer, La Banque Royale du Canada and Provigo-Loblaws.

None of these organizations are involved in the research conducted by Dr Lamarche and his team.

Dr Lamarche has received funding in the last 5 years from the Canadian Institutes for Health

Research, the Natural Sciences and Engineering Research Council of Canada, Agriculture and Agri-

Food Canada (Growing Forward program supported by the Dairy Farmers of Canada (DFC), Canola

Council of Canada, Flax Council of Canada, Dow Agrosciences), Dairy Research Institute, Dairy

Australia, Merck Frosst and Atrium Innovations. All support is investigator initiated, with no

influence of the organizations in defining the research questions, in the process related to data

analysis and interpretation, and publication of results. J-ML: Works for CNIEL, YOPLAIT,

SYNDIFRAIS, LACTALIS, Alliance 4, LESAFFRE, member of scientific advisory board APRIFEL, ENSA,

FICT, OCAH, IOT. PL: None. MM: Receipt of honorarium and travel expenses for presentations

given at conferences organized by the Dairy Council for Northern Ireland and the European Milk

Forum. MCM: Paid consultancies for CNIEL (French Dairy Interbranch Sector) and for different

food and dairy companies, research laboratory received funding from CNIEL (French Dairy

Interbranch Sector), Sodiaal-Candia R&D, Nutricia Research, Danone Research, and received

supply of 1 PhD student from ITERG (Industrial Technical Centre for the oils and fats business

sector, France). Member of the Scientific Committee of ITERG (Industrial Technical Centre for the

oils and fats business sector, France) (non-financial interest). DM: None. SS-M: received funding

from the Global Dairy Platform, Dairy Research Institute and Dairy Australia for a meta-analysis on

cheese and blood lipids (2012) and a meta-analysis of dairy and mortality (2015). She received The

Wiebe Visser International Dairy Nutrition Prize from the Dutch Dairy Association’s (NZO) Utrecht

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Group. In 2017, a students’s internship project was partly funded by the Dutch Dairy Organization

and Global Dairy Platform.

Licence

The Corresponding Author has the right to grant on behalf of all authors and does grant on behalf

of all authors, an exclusive licence (or non exclusive for government employees) on a worldwide

basis to the BMJ Publishing Group Ltd (“BMJ”), and its Licencees to permit this article (if accepted)

to be published in The BMJ’s editions and any other BMJ products and to exploit all subsidiary

rights, as set out in BMJ licence.

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