The nutritional challenges around bread -

why bread remains a healthy part of the daily diet

Luud Gilissen

FEDIMA & AIBI, Brussels, 13th April 2016

Context 1: Health care costs

Price-increases of health care costs

● Health care budget in NL: ~100 B€/year

Price-increases of medicines (€/$) (some examples)

● Daraprim (antidepressivum): 1,- 13.50 750.- (1 tablet)

● Parnate (antidepressivum): 110.- 1,500,- (per month)

● Lemtrada (leukemia multiple sclerosis): x 40

● Cycloserine (tuberculose): 500,- 10,800.- 1,050

Are all medicins necessary and healthy?

● Paroxetine (antidepressivum) is not effective but gives only strong and

harmful side-effects and is suspect (600.000 users in NL over 14 years)

● Where does quackery start?

Context 1: Pharma

Strong interconnections:

Pharma Health Insurance Comp

Hospitals Government

Strong lobby:

● Pharma EU

How to reduce health care costs?

Context 1: Reducing Health Care Costs

Much more focus on prevention

Promotion of healthy food (and life style) as natural medicines

But:

Context 1: Our Food World today (the illusion of choice)

They all use refined wheat and wheat

derivatives (as also do most bakers) in

many of their products

bran (outer layer of the grain)

vital wheat gluten

germs; flour fractions

native and modified starch

grain alcohol

bioethanol

crystalline polyols

liquid polyols glucose syrups

maltodextrins

starch milk

Context 1: Economics of wheat (and corn): starch

‘whole grain’?

milling and separation; sieving; mixing

Playing field for prevention

Help!

Context 1:Healthy food

Whole-grain (bran containing) food (Fardet 2010; Huang et al 2015; Wu et al 2015)

May come from the bakery sector

Awareness in the sector?

Human health: which are the issues?

Chronic diseases:

● Cardiovascular diseases

● Diabetes

● Obesity

● Cancer

● Respiratory diseases

● Immune-related diseases

● Allergies

● Coeliac disease

● Food sensitivities

● Non-Coeliac Wheat/Gluten Sensitivity (NCW/GS)

Easy to prevent

Avoidance of tobacco

Healthy diet

Regular physical activity

‘Whole grain’ can contribute

Content

Wheat-related disorders:

● Obesity; Type 2 Diabetes

● Allergy; Sensitivity; Intolerance

Focus on prevention: Plant and food-technological approaches

Focus on health: Fibres and beyond

Conclusions

Obesity; T2Diabetes; NCG/WSensitivity

New health threats?

● Obesity and T2D: yes, but independent of wheat

● NCG/WS: questionable

Increasing demand for gluten-free diet during the last

decade may reflect the impact

Relationship to

● Refined wheat products: possible

Genetic/immune Relationship

Unknown

Context 2 - History of cereal consumption

Something wrong with cereal consumption?

Fossil records: Agriculture started ~10.000 ya, but:

● ~6 Mya: Early hominids diverged from apes due to specialized feeding on small and hard grass (cereal) seeds (molar shape and thick enamel) (Straight, 1997; Sponheimer & Lee-Thorpe, 1999; Senut at al 2001)

● ~1.5 Mya: Homo sp increased the fraction of C4-based resources (= cereals) in the diet (Cerling et al 2013)

● 120.000 ya: meeting of Neanderthals and modern humans in the Levant (Iran/Iraq region) where wheat and barley species are endemic (Kuhlwilm et al 2016)

● 50.000 ya: Neanderthals consumed cooked barley (Henry et al 2011)

● 32,600 ya: thermal pretreatment and grinding of oat seeds (Italy) (Lippi et al 2015)

● 15,000 ya: barley groat meals and porridge; and 13,500 ya: unleavened bread from fine barley flour (Eitam 2015)

● 11,000 ya: ground collection of wild barley and wild wheat as intermediate step between seed collecting by hunter-gatherers and cereal harvesting by early farmers (Kislev, 2003)

● 10-8.000 ya: development of hexaploid (AABBDD genome) bread wheat and spelt wheat from hybridisations of tetraploid emmer wheat (AABB) and T. tauschii (DD)

Major cereal allergies

Wheat allergy (world-wide; 0.25%)

Maize allergy (S-EU, Mexico, USA; <<)

Rice allergy (Asia; <<)

Cereal allergy is rare

Wheat sensitization is high (2%)

Wheat contains ~30 IgE-responding antigens from different protein families

No clinical symptoms

Allergic (IgE)

NCW/GS:Which compounds involved?

Gluten? ATIs? FODMaPs? Combi? None?

Functional bowel complaints

● Mainly self-diagnosed

● Rapidly rising (~5-10% in USA and UK)

● Mainly in women in the age group of 30-50 years

● Genetic predisposition still unknown

● No biomarkers known

● In IBS, 30% improves on ‘gluten-free’ and ‘FODMaP’-low diet (including ‘wheat-free’)

● Improvement includes ‘feeling better’

● Real prevalence (according to The Salerno Experts’ Criteria): >1%

Genetic/immune Relationship

Unknown

gluten

amylase trypsine inhibitors

The War on Wheat (Brouns, Gilissen, Shewry, Van Straaten)

Unsubstantiated wheat and gluten related health concerns are damaging the cereal foods sector and compromising public health

Health Grain Forum: intervention study under construction regarding cereal and gluten avoidance (start 2016)

● ‘Analysis of effects of food processing (yeast vs sourdough fermentation) on wheat compounds (gluten, ATIs, FODMAPS) and their impact on bowel symptoms and wellness complaints’

● Focus on IBS

● Also Placebo and Nocebo effects will be measured

Coeliac disease (CD)

Chronic inflammation of the small

intestine

● Increased 4x during the last 50 years (current prevalence: 0.5-2%)

● Genetic predisposition (HLA-DQ2/8)

● Gluten (seed storage proteins) from wheat, rye and barley

● Underestimated (only 10-20% diagnosed)

Major symptoms of CD in children Chronic bowel ache and diarrhoea Growth retardation

Major symptoms of CD in adults Chronic fatigue, headache, bowel complaints Reduced fertility; miscarriage Dermatitis herpetiformis Osteoporosis Deafness Neuropathy Intestinal cancer (lymphoma)

Auto-immune (T-cells)

Strict and life-long glutenfree diet

Is wheat the only cause of CD and NCGWS?

Tolerance-breaking factors may be found in

● Overall feeding pattern

● Smoking during pregnancy

● Hygiene and drinking water quality

● Urban versus rural life style

● Composition (quantity and and quality) of the gut microflora

Unbalanced interaction of human genotype, diet/environment and intestinal microbiota may largely determine the individual’s intolerance/sensitivity

Astronomical system of wheat/gluten related disorders

1%

1%

Strategies for reducing the incidences of CD and NCW/GS should

aim at:

Underestimated population with CD

(only 10-20% has been diagnosed)

Gluten-free, Wheat-free

Self-overestimated population of NCW/GS

Plant and Food-technological approaches

Plant-related strategies

Selection of low-CD-immunogenic wheat lines (resulted in a

few reduced-immunogenic AABB lines)

New synthetic hexaploids (AABB + new DD: bread wheat-like lines with

reduced immunogenicity)

Deletion of specific chromosome parts (carrying gluten genes)

Traditional breeding (barley)

RNAi (GM) (silencing gliadin genes) *

Mutation breeding (non GM) and Genome editing (GM?) (targeted epitope modification) *

RNA-interference (RNAi): construct (GM)

RNAi: effects

Gil-Humanes et al 2014

RNAi: baking quality

Gil-Humanes et al 2014

Mutation breeding: gliadin mutagenesis

New collaborative project of PRI with NIAB (UK) (Jouanin, PhD), Barro (Spain), Chen (Nanchang) (Chinese student with Koning LUMC)

Objectives

● Gliadin epitope point mutations Prevention of HLA-DQ receptor

binding

● DNA fragment loss in gliadin gene family Decrease gene copy number

Approaches

● Chemical mutagenesis (EMS): Gliadin sequenses available for epitope testing (with UC Davis, CA) [Non GM]

● Gamma-ray mutagenesis: Population of lines available for gliadin testing (with John Innes, UK) [Non GM]

● Targeted mutagenesis (CRISPR/Cas9 method): Gene construct Transformation of embryonic cells Specific targeting of gliadin epitopes Mutation Deletion of construct [GM status pending]

EMS

Gamma-ray

CRISPR/Cas9

Food related strategies

Reduction of vital gluten *

Elimination of gliadin from gluten *

Sourdough *

Malting

Patient-specific epitope sensitivity profile

The gluten contamination elimination diet (GCED)

Helminth-based therapy

Reduction of vital gluten

Vital gluten: by-product in starch industry

Large-scale application as bread improver: ... gives whole grain loaves a ‘boost’ ...

.... Other factors, such as per capita vital gluten intake, variations in individual diets with regard to the amount and types of wheat consumed, wheat genetics, and agronomic practices (such as nitrogen fertilization), that affect protein content might contribute to determining the “toxicity” of wheat for people with the appropriate genetic susceptibility for celiac disease ... (Kasarda 2013)

Elimination of gliadin from gluten

Will industrial separation be possible?

Will technological quality be maintained?

Labscale (Van den Broeck et al, pers. comm):

Sourdough bread

Sourdough bread seems safe to CD patients?

● Breakdown of resistant peptides (e.g. 33-mer) (Greco et al., 2011)

● More research is needed to confirm this claim

Low prevalence of CD in Germany: due to high consumption

of sourdough bread?

● 0.3% in Germany; 2.4% in Finland (Mustalahti et al., 2010)

Focus on whole grain and disease prevention

Fibres: improved faecal bulking and satiety, viscosity and SCFA production, reduced glycaemic response

● Wu et al 2015: Higher whole grain (especially bran)

consumption is associated with lower CVD mortality in US man

and women, independent of other dietary and lifestyle factors

(1984-2010 in cohorts of 74,341 women and 43,744 men)

● Huang et al 2015: Increased consumption of whole grains and

cereal fibre was associated with reduced total and cause-

specific mortality (cancer, CVD, diabetes, respiratory disease,

infections, etc). Cereal fibre accounts for the protective effects

of whole grains on mortality (1995-2009 in cohort of 367,442

participants)

Focus on whole grain and disease prevention

Beyond fibres: Fardet 2010 (relevant examples):

● Mg improved glycaemic homeostasis (increased

insulin secretion)

● Bran: minerals, trace-elements, vitamins, carotenoids,

polyphenols, alkylrecorcinols anti-oxidant and anti-

carcinogenic

● Whole grain: methyl donors and lipotropes DNA

protection, fat break down, cardiovascular and liver

protection; sulfur compounds, lignin, phytic acid

anti-oxidant protection; B-complex vitamins

nervous system, mental health;

Whole grain: Dutch Health Council (schijf van vijf)

Alternative grains:

Traditional wheat species

● T. monococcum (Einkorn): only AA genome

● Variety ‘Monlis’ was safe in coeliac food challenge (Zanini et al 2013)

● T. turgidum (Emmer): AABB genome

● Some varieties no coeliac T cell proliferation (Vincentini et al 2009)

● T. spelta (Spelt wheat): AABBDD

● Low in FODMaPS (Biesiekierski et al 2011)

● No/less complaints in IBS cases (Van Buul 2015)

Alternative grains:

Oats

● No coeliac-immunogenic epitopes (Londono et al 2014); low in FODMaPs (Biesiekierski et al 2011)

● Rapidly increasing interest and consumption by CD consumers

(promoted by NCV) and consumers in general

Gluten-free oat bread - FreeOf

Conclusions

Bakery sector can play a crucial role

● in health promotion and disease prevention

● in reducing health care costs

Challenges and Responsibilities with breeders, farmers, food industries, bakery organisations (FEDIMA; AIBI), retail, research organisations, governments and consumers (agro-food chain)

Focus on Whole grain (bran) and Sourdough

Thanks

Celiac Disease Consortium (2004-2013)

● Frits Koning

PRI – Wageningen UR

● Hetty van den Broeck Jan Cordewener Twan America Ingrid van der Meer Jan Schaart Elma Salentijn Diana Londono Aurelie Jouanin René Smulders Ed Hendrix

EU TraFooN

● Susanne Braun; Javier Casado

Refs:

Gilissen LJWJ, Van der Meer IM, Smulders MJM (2014) Reducing the incidence of allergy and intolerance to cereals. Journal of Cereal Science 59: 337-353

Smulders MJM, Jouanin A, Schaart J, Visser RGF, Cockram J, Leigh F, Wallington E, Boyd LA, Van den Broeck HC, Van der Meer IM, Gilissen LJWJ (2015) Development of wheat varieties with reduced contents of coeliac-immunogenic epitopes through conventional and GM strategies. Proceedings of the 28th PWG Meeting, Nantes, pp 47-56

Gilissen LJWJ, Van der Meer IM, Smulders MJM (2016) Strategies to reduce or prevent wheat coeliac-immunogenicity and wheat sensitivity through food. Proceedings of the 29th PWG Meeting, Tulln, pp 41 -54