Confidential: For Review Only · Research Institute & UCSF Benioff Children's Hospital Oakland, USA, [email protected]. Benoît Lamarche, Chair of Nutrition, Institute of Nutrition

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

fatty acids: time for a new approach?

Journal: BMJ

Manuscript ID BMJ-2018-047667.R1

Article Type: Analysis

BMJ Journal: BMJ

Date Submitted by the Author: 13-Dec-2018

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

1

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

Page 1 of 20


BMJ

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960

mailto:[email protected]




















2

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.

Page 2 of 20


BMJ

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960


3

Introduction

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

the 54.7 million deaths in 2016 (2). Cardiovascular diseases (CVD) are responsible for

approximately 45% of all NCD deaths. Modifiable risk factors such as diet, physical activity,

smoking, and alcohol intake, are 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 (1). 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 EU. In the US the FDA 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 (PUFA) and monounsaturated fat (MUFA), to reduce CVD incidence and

mortality (1). This recommendation fails 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 (3-5) (Box 1).

Page 3 of 20


BMJ

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960


4

Box 1. SFA are contained in a range of very different food products

SFA are found in a wide diversity of foods, which vary in both composition and structure (6),

resulting in completely different physiological effects. Butter is a water-in-oil emulsion, while

SFA-rich vegetable oils (e.g. palm oil, coconut oil), lard and tallow are 100% lipids. Full-fat milk is

a natural emulsion of fat globules, covered by their biological milkfat globule membrane

(MFGM). In homogenized milkfat droplets are much smaller and covered by milk proteins.

Yogurt is a fermented food with live cultures, in which milkfat globules are dispersed in the

gelled milk protein matrix. Cheese is one of the most complex dairy matrixes. It is a fermented

food with live cultures, where fat is present within milkfat globules, and sometimes free fat

inclusions in a more or less solid matrix rich in milk proteins, calcium and MFGM. Hard cheeses

are the most nutrient-rich. Ice cream contains a combination of crystallized fat globules around

air bubbles, and ice crystals in a liquid syrup phase. In unprocessed meat, lipids are mostly

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

contain fat inclusions (of µm to mm size) in 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. Chocolate is composed of particles (e.g. sugar, fermentation products

from cocoa bean) embedded in solid fat. In foods such as pastries, cookies etc. the fat inclusions

(composed of palm oil, butter etc.) are embedded within a more or less solid, often sugar-rich,

carbohydrate matrix.

These different food matrixes also carry SFA within different types of lipid molecules - notably

triglycerides and phospholipids. In all animal sources (dairy, meat and eggs) most SFA are

esterified within triglycerides, but a small proportion of SFA is esterified within biological/cell

membrane phospholipids. In these molecules SFA can be esterified at different positions

Page 4 of 20


BMJ

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960


5

depending on fat/oil source. Food matrix modulates lipid digestion, absorption kinetics, and

postprandial lipemia (6), an independent CVD risk factor (7).

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). By contrast, a Cochrane analysis that only included data from 15 RCTs

found an association between a composite end-point, “combined cardiovascular events”, and

reducing SFA intake [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 (MI), 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). Using surrogate end-points as

evidence for a beneficial clinical effect of replacement of total SFA from all food sources with PUFA

is problematic for a number of reasons:

First, de focusing on total SFAs as the modifying factor is problematic because the magnitudes and

even directions of these effects vary depending on the specific SFA studied e.g. ranging from lauric

acid (12 carbons) to stearic acid (18 carbons).

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

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

included trials compared the effect of consuming diets supplemented with specific fats compared

Page 5 of 20


BMJ

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960


6

to consumption of specific plant oils such as corn or soybean oil, rather than investigating whole

food sources of SFA (12).

Using LDL-cholesterol concentration alone as a marker of diet effects on CVD risk also has

limitations, as atherogenecity of the LDL-particles is also determined by resistance against

oxidation, size, density, composition, cytotoxicity, and presence or absence of other lipoproteins

such as apolipoprotein CIII. There is evidence that the increase in LDL-cholesterol from total SFA

consumption is paralleled by increases in LDL-particle size, a change that is not consistent with

increased risk of CVD (13). Effects of total SFA and individual SFA on apolipoprotein CIII are not

established (14).

A broader view on biomarkers of CVD is needed, as illustrated by the PURE study of over 100,000

people, which found that SFA are associated with higher LDL-cholesterol, but also with higher HDL

and lower triglycerides, and lower ApoB/ApoA ratio. The latter marker reflects the small, dense

LDL-particles that are more atherogenic than LDL-cholesterol alone, and are the strongest risk

marker for MI and stroke. Saturated fat was found to be associated with lower (protective)

ApoB/ApoA ratio, while carbohydrates were associated with higher ratios (15). Relying on a

pooled effect on LDL-cholesterol of total SFA from all food sources to predict changes in CVD risk is

not evidence-based.

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

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

meta-analyses of prospective cohort studies, arguing that the quality of evidence for relevant

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

differential effects of replacing SFA with different nutrients (8,9,16). However, observational

studies are valuable for assessing the association of SFA with CVD end-points, and are particularly

useful for food-based analyses.

Page 6 of 20


BMJ

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960


7

A 2010 consensus panel on saturated fats concluded “There is increasing evidence to support that

the total matrix of a food is more important than just its fatty acid content when predicting the

effect of a food on CHD risk … ” (16).

Evidence linking foods high in saturated fat to cardiovascular disease

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. High quality prospective, population-based studies and a number of meta-analyses have

found that higher egg consumption is not associated with risk of CHD, and is associated with lower

risk of stroke; subgroup analyses based on a small number of studies found higher CHD risk in

diabetic populations (17,18). RCTs have, however, found neutral or beneficial effects on markers

of diabetes and CVD. One trial comparing the effects of a high-egg diet (12 eggs/wk) with a low-

egg diet (<2 eggs/wk) on lipid profiles in 140 overweight or obese people with prediabetes or type

2 diabetes for 12 months found no effects on total cholesterol, HDL- or LDL-cholesterol,

triglycerides, or glycaemic control (19).

Dark chocolate

Dark chocolate also contains substantial amounts of SFA, but mainly stearic acid, which has a

neutral effect on CVD risk. 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 can be beneficial for health, including potential anti-oxidative, anti-hypertensive,

Page 7 of 20


BMJ

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960


8

anti-inflammatory, anti-atherogenic, and anti-thrombotic properties, as well as preventive effects

on CVD and diabetes (20-23). The WHO draft guidelines that stearic acid has no harmful effect on

’any outcome assessed’ yet does 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 (RR =

0.96, 95%CI = 0.93, 0.99; P = 0.021) (24).

Yogurt and cheese

Dairy products are the major source of SFA in most global diets, and they are one of the main

targets of the WHO to reduce intake of SFA. However, dairy is also a major source of protein,

calcium, and other nutrients. Yogurt is fermented and often contains added probiotics; cheese is

fermented, often ripened. Most major dietary guidelines recommend dairy products as part of a

healthy diet, but recommend low-fat/fat-free versions to reduce SFA intake. 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 (25Indeed,

both mechanistic research and observational studies find that whole-fat fermented dairy, e.g.

cheese and yogurts, may actually reduce CVD and diabetes risk (25-28). High plasma levels of the

SFA C 17:0, which primarily originates from dairy, have been associated with a reduced risk of

CHD (29); while SFA 15:0, SFA 17:0, and the natural ruminant trans-16:1n7 are not associated with

higher risk of total mortality (28). Moreover, a pooled individual-level analysis of nearly 65,000

Page 8 of 20


BMJ

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960


9

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

(30).

Among dairy products, cheese has highest fat content yet has small effects on LDL-cholesterol

(31). A meta-analysis of RCTs found that cheese intake lowers total cholesterol, LDL-cholesterol,

and HDL-cholesterol, compared with butter (32). A number of meta-analyses found no adverse

association between milk, cheese, yogurt, or total dairy intake and CVD, CHD, or stroke, regardless

of fat content (33, 34). Recent meta-analyses have found that cheese and yogurt intakes are

inversely associated with CVD risk, and that a high intake of cheese is associated with an 8% lower

risk of CHD, and a 13% lower risk of stroke (34). Whole-fat dairy may play a particular role in the

prevention of type 2 diabetes, a known risk factor for CVD (14, 35-37).

Cheeses and yogurts consist of complex food matrices and ingredients with diverse biological

effects. Major components include different fatty acids, proteins (whey and casein), minerals

(calcium, magnesium, phosphate), sodium, and phospholipid components of milk fat globule

membrane (MFGM) (38). 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 (38, 39). Other non-

homogenized whole-fat dairy products are also typically rich in MFGM. 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). Indeed, cheese is a major

dietary source of the latter.

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

Page 9 of 20


BMJ

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960


10

of processed meat, but not red meat, was associated with a higher risk of CHD (40). Another meta-

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

servings of meat (41). Prospective cohorts also suggest stronger associations of processed meat

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

meta-analysis reported that whilst processed meat gave rise to a 19% higher risk of type 2

diabetes, red meat consumption was not significantly associated (41). The EPIC-InterAct study,

with 340,234 adults from eight European countries, found positive associations between type 2

diabetes and increasing intake of total meat, largely related to processed meat consumption (42).

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 (43, 44).

Conclusions

Thus, 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 wherein preservatives and heme contents appear to be more relevant.

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. Dietary guidelines should

not take a simple nutrient-based view. The WHO SFA guidelines should consider different types of

fatty acids and, more importantly, the diversity of foods containing SFA that may be harmful,

Page 10 of 20


BMJ

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960


11

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.

Page 11 of 20


BMJ

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960


12

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

Page 12 of 20


BMJ

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960


13

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

Page 13 of 20


BMJ

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960


14

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.

Page 14 of 20


BMJ

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960


15

References

1. WHO. Draft guidelines on saturated fatty acid and trans-fatty acid intake for adults and children.

Public Consultation May – June 2018.

https://extranet.who.int/dataform/upload/surveys/666752/files/Draft%20WHO%20SFA-

TFA%20guidelines_04052018%20Public%20Consultation(1).pdf

2. GBD 2016 Causes of Death Collaborators. Global, regional, and national age-sex specific

mortality for 264 causes of death, 1980-2016: a systematic analysis for the Global Burden of

Disease Study 2016. Lancet 2017;390(10100):1151–210.

3. Mozaffarian D, Rosenberg I, Uauy R. History of modern nutrition science—implications for

current research, dietary guidelines, and food policy. BMJ 2018;361:k2392

4. Mozaffarian D, Forouhi NG. Dietary guidelines and health—is nutrition science up to the task?

BMJ 2018;360:k822

5. Forouhi NG, Krauss RM, Taubes G, Willett W. Dietary fat and cardiometabolic health: evidence,

controversies, and consensus for guidance. BMJ 2018;361:k2139

6. Michalski MC, Genot C, Gayet C, et al.; Steering Committee of RMT LISTRAL. Multiscale

structures of lipids in foods as parameters affecting fatty acid bioavailability and lipid metabolism.

Prog Lipid Res 2013;52:354-73. doi: 10.1016/j.plipres.2013.04.004.

7. Pirillo A, Norata GD, Catapano AL. Postprandial lipemia as a cardiometabolic risk factor. Curr

Med Res Opin 2014;30(8):1489-503. doi: 10.1185/03007995.2014.909394.

8. de Souza RJ, Mente A, Maroleanu A, et al. Intake of saturated and trans unsaturated fatty acids

and risk of all cause mortality, cardiovascular disease, and type 2 diabetes: systematic review and

meta-analysis of observational studies. BMJ 2015 Aug 11;351:h3978.

9. Siri-Tarino PW, Sun Q, Hu FB, Krauss RM. Meta-analysis of prospective cohort studies evaluating

the association of saturated fat with cardiovascular disease. Am J Clin Nutr 2010 Mar; 91(3): 535–

546.

Page 15 of 20


BMJ

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960

https://extranet.who.int/dataform/upload/surveys/666752/files/Draft%20WHO%20SFA-TFA%20guidelines_04052018%20Public%20Consultation(1).pdf

https://extranet.who.int/dataform/upload/surveys/666752/files/Draft%20WHO%20SFA-TFA%20guidelines_04052018%20Public%20Consultation(1).pdf


16

10. Ramsden CE, Zamora D, Majchrzak-Hong S et al. Re-evaluation of the traditional diet-heart

hypothesis: analysis of recovered data from Minnesota Coronary Experiment (1968-73). BMJ. 2016

Apr 12;353:i1246. doi: 10.1136/bmj.i1246.

11. Hooper L, Martin N, Abdelhamid A, Smith DG. Reduction in saturated fat intake for

cardiovascular disease. Cochrane Database Syst Rev 2015;6:CD011737.

12. Mensink, RP. Effects of saturated fatty acids on serum lipids and lipoproteins: a systematic

review and regression analysis. Geneva: World Health Organization 2016. ISBN 978 92 4 156534 9.

13. Siri-Tarino PW, Chiu S, Bergeron N, Krauss RM. Saturated fats versus polyunsaturated fats

versus carbohydrates for cardiovascular disease prevention and treatment. Ann Rev Nutr

2015;35:517-43. doi: 10.1146/annurev-nutr-071714-034449.

14. Taskinen MR, Borén J. Why is apolipoprotein CIII emerging as a novel therapeutic target to

reduce the burden of cardiovascular disease? Curr Atheroscler Rep 2016;18:59.

15. Mente A, Dehghan M, Rangarajan S, et al.; Prospective Urban Rural Epidemiology (PURE) study

investigators. Association of dietary nutrients with blood lipids and blood pressure in 18 countries:

a cross-sectional analysis from the PURE study. Lancet Diabetes Endocrinol 2017;5:774-787.

16. Astrup A, Dyerberg J, Elwood P, et al. The role of reducing intakes of saturated fat in the

prevention of cardiovascular disease: where does the evidence stand in 2010? Am J Clin Nutr

2011;93:684-688.

17. Rong Y, Chen L, Zhu T, et al. Egg consumption and risk of coronary heart disease and stroke:

dose-response meta-analysis of prospective cohort studies. BMJ 2013;346:e8539.

18. Geiker NRW, Larsen ML, Dyerberg J, Stender S, Astrup A. Egg consumption, cardiovascular

diseases and type 2 diabetes. Eur J Clin Nutr 2018;72:44-56.

19. Fuller NR, Sainsbury A, Caterson ID, et al. The effect of a high-egg diet on cardiometabolic risk

factors in people with type 2 diabetes: the DIABEGG study—randomized weight loss and follow-

up. Am J Clin Nutr 2018;107:921–31.

Page 16 of 20


BMJ

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960


17

20. Buitrago-Lopez A, Sanderson J, Johnson L, et al. Chocolate consumption and cardiometabolic

disorders: systematic review and meta-analysis. BMJ 2011;343:d4488. doi: 10.1136/bmj.d4488.

21. Larsson SC, Åkesson A, Gigante B, Wolk A. Chocolate consumption and risk of myocardial

infarction: a prospective study and meta-analysis. Heart 2016;102:1017-22. doi: 10.1136/heartjnl-

2015-309203.

22. Gianfredi V, Salvatori T, Nucci D, Villarini M, Moretti M. Can chocolate consumption reduce

cardio-cerebrovascular risk? A systematic review and meta-analysis. Nutrition 2018;46:103-114.

doi: 10.1016/j.nut.2017.09.006.

23. Yuan S, Li X, Jin Y, Lu J. Chocolate consumption and risk of coronary heart disease, stroke, and

diabetes: a meta-analysis of prospective studies. Nutrients 2017;9 pii:E688. doi:

10.3390/nu9070688.

24. Pimpin L, Wu JHY, Haskelberg H, Del Gobbo L, Mozaffarian D. Is butter back? A systematic

review and meta-analysis of butter consumption and risk of cardiovascular disease, diabetes, and

total mortality. PLoS ONE 2016;11:e0158118. doi:10.1371/journal.pone.0158118.

25. Dehghan M, Mente A, Rangarajan S et al. /Prospective Urban Rural Epidemiology (PURE) study

investigators. Association of dairy intake with cardiovascular disease and mortality in 21 countries

from five continents (PURE): a prospective cohort study. Lancet 2018;392(10161):2288-2297. doi:

10.1016/S0140-6736(18)31812-926. Ibsen DB, Laursen ASD, Lauritzen L, Tjønneland A, Overvad K,

Jakobsen MU. Substitutions between dairy product subgroups and risk of type 2 diabetes: the

Danish Diet, Cancer and Health cohort. Br J Nutr 2017;118:989-997. doi:

10.1017/S0007114517002896.

27. Astrup A. Yogurt and dairy product consumption to prevent cardiometabolic diseases:

epidemiologic and experimental studies. Am J Clin Nutr 2014;99(5 Suppl):1235S-42S.

Page 17 of 20


BMJ

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960


18

28. de Oliveira Otto MC, Mozaffarian D, Kromhout D, et al. Dietary intake of saturated fat by food

source and incident cardiovascular disease: the Multi-Ethnic Study of Atherosclerosis. Am J Clin

Nutr 2012;96:397-404. doi: 10.3945/ajcn.112.037770

29. Chowdhury R, Warnakula S, Kunutsor S, Crowe F, Ward HA, Johnson L, et al. Association of

dietary, circulating, and supplement fatty acids with coronary risk: a systematic review and meta-

analysis. Ann Intern Med 2014;160(6):398-406.

30. Imamura F, Fretts A, Marklund M, et al.; Fatty Acids and Outcomes Research Consortium

(FORCE). Fatty acid biomarkers of dairy fat consumption and incidence of type 2 diabetes: A

pooled analysis of prospective cohort studies. PLoS Med 2018 Oct 10;15(10):e1002670. doi:

10.1371/journal.pmed.1002670.

31. Hjerpsted J, Leedo E, Tholstrup T. Cheese intake in large amounts lowers LDL-cholesterol

concentrations compared with butter intake of equal fat content. Am J Clin Nutr 2011;94:1479-

1484.

32. de Goede J, Geleijnse JM, Ding EL, Soedamah-Muthu SS. Effect of cheese consumption on

blood lipids: a systematic review and meta-analysis of randomized controlled trials. Nutr Rev

2015;73:259-275.

33. de Goede J, Soedamah-Muthu SS, Pan A, Gijsbers L, Geleijnse JM. Dairy consumption and risk

of stroke: a systematic review and updated dose-response meta-analysis of prospective cohort

studies. J Am Heart Assoc 2016;5:10.1161/JAHA.115.002787.

34. Guo J, Astrup A, Lovegrove JA, Gijsbers L, Givens DI, Soedamah-Muthu SS. Milk and dairy

consumption and risk of cardiovascular diseases and all-cause mortality: dose-response meta-

analysis of prospective cohort studies. Eur J Epidemiol 2017;32:269-287. doi: 10.1007/s10654-017-

0243-1.

Page 18 of 20


BMJ

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960


19

35. Ibsen DB, Laursen ASD, Lauritzen L, Tjønneland A, Overvad K, Jakobsen MU. Substitutions

between dairy product subgroups and risk of type 2 diabetes: the Danish Diet, Cancer and Health

cohort. Br J Nutr 2017;118:989-997. doi: 10.1017/S0007114517002896.

36. de Souza RJ, Mente A, Maroleanu A, et al. Intake of saturated and trans unsaturated fatty acids

and risk of all cause mortality, cardiovascular disease, and type 2 diabetes: systematic review and

meta-analysis of observational studies. BMJ 2015;351:h3978. doi: 10.1136/bmj.h3978

37. Harcombe Z, Baker JS, Davies B. Evidence from prospective cohort studies does not support

current dietary fat guidelines: a systematic review and meta-analysis. Br J Sports Med

2017;51:1743-1749. doi: 10.1136/bjsports-2016-096550.

38. Thorning TK, Raben A, Tholstrup T, Soedamah-Muthu SS, Givens I, Astrup A. Milk and dairy

products: good or bad for human health? An assessment of the totality of scientific evidence. Food

& Nutrition Research 2016;60:32527. doi:10.3402/fnr.v60.32527.

39. Thorning TK, Bertram HC, Bonjour JP, et al. Whole dairy matrix or single nutrients in

assessment of health effects: current evidence and knowledge gaps. Am J Clin Nutr

2017;105:1033-1045. doi:10.3945/ajcn.116.151548.

40. Micha R, Wallace SK, Mozaffarian D. Red and processed meat consumption and risk of incident

coronary heart disease, stroke, and diabetes mellitus: a systematic review and meta-analysis.

Circulation 2010;121:2271-2283.

41. O’Connor LE, Kim JE, Campbell WW. Total red meat intake of ≥0.5 servings/d does not

negatively influence cardiovascular disease risk factors: a systemically searched

meta-analysis of randomized controlled trials. Am J Clin Nutr 2017;105:57–69.

42. The InterAct Consortium. Association between dietary meat consumption and incident type 2

diabetes: the EPIC-InterAct study. Diabetologia 2013;56:47–59.

Page 19 of 20


BMJ

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960


20

43. Sandoval-Insausti H, Pérez-Tasigchana RF, López-García E, García-Esquinas E, Rodríguez-

Artalejo F, Guallar-Castillón P. Macronutrients intake and incident frailty in older adults: a

prospective cohort study. J Gerontol A Biol Sci Med Sci 2016;71:1329–1334.

44. Struijk EA, Banegas JR, Rodríguez-Artalejo F, Lopez-Garcia E. Consumption of meat in relation

to physical functioning in the Seniors-ENRICA cohort. BMC Medicine 2018;16:50.

Page 20 of 20


BMJ

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960

Documents

Confidential: For Review Only · Research Institute & UCSF Benioff Children's Hospital Oakland, USA, [email protected]. Benoît Lamarche, Chair of Nutrition, Institute of Nutrition