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
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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 (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).
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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
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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
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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.
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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,
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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
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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
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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,
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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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