Luud Gilissen · (Brouns, Gilissen, Shewry, Van Straaten) Unsubstantiated wheat and gluten related...
Transcript of Luud Gilissen · (Brouns, Gilissen, Shewry, Van Straaten) Unsubstantiated wheat and gluten related...
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
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) *
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;
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