Pierre MADL Div. of Material Sciences Dep

Transcription

Quality of our Food
15-08-21
15-08-21
Madl
Madl
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Pierre MADL
Div. of Material Sciences
Dep. Physics & Biophysics
University of Salzburg
Hellbrunnerstr. 34
A-5020 Salzburg
[email protected]
http://biophysics.sbg.ac.at/home.htm
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Intro
Food
Epigenome
Method
Implication
Intro
Points of Departure
1. Psychological and physical conditions;
2. Personal life attitude;
3. Personal life organization;
4. Epi-/Genetic predisposition;
5. Nutrition
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p.21: »das ganze ist mehr als die summe seiner teile«. Kollath (1977) meint, dass nahrung mehr
als nur das gemisch aus kohlehydraten, fetten, eiweissen, mineralsalzen, vitaminen,
spurenelementen und ballaststoffen ist …. Legionen von forschern könnten jahrzehntelang mit
dieser fragestellung sinnvoll beschäftigt werden; d.h.:
- in wie weit biologische rhythmen die optimale auswahl der nahrung beeinflussen (wie es bspweise die mazdaznan-filosofie postuliert),
- ob es zutrifft, dass das optimum der ernährung gleichbedeutend damit ist, dass möglichst wenig
nahrung aufgenommen werden muss,
- ob die optimale nahrung stets aus der jeweiligen lebensregion des verbrauchers stammen muss,
wie es die makrobiotiker annehmen,
- ob polaritätsdenken eine basis hat, bsp-weise ob die ernährungsfysiologische rolle der
einzelkomponenten das säure-basen-gleichgewicht des bluts, des urins und des extrazellulärraums eine übergeordnete funktion hat,
- inwieweit den lebensmitteln vorwiegend eine evolutionsbiologische bedeutung zukommt, wie es
in ansätzen der anthroposofen zum ausdruck kommt.
Heute kennt man fast alle mangelerscheinungen, die beim ausfall »essentieller« substanzen in der
nahrung auftreten. Weniger gut bekannt sind die langzeit-wirkungen von überschüssen …. In
form von stärkungsmitteln, vitaminpräparaten oder »natürlichen« zusatzstoffen in der nahrung
….. Der gesunde appetit nimmt jedenfalls wenig rücksicht darauf. …. »Bei durstgefühl ist es
mit hoher wahrscheinlichkeit günstig zu trinken.« fragt sich nur noch, was.
Source: Poop F.A. (2002). Die Botschaft der Nahrung, Zweitausendeins Verlag, FRA.a.Main FRG
Kollath W. (1997). Die Ordnung unserer Nahrung. 6th ed. K. F. Haug Verlag, Heidelberg – FRG.
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Intro
Food
Epigenome
Method
Implication
Threshold Levels
Threshold & Risks:
• Threshold limits
• No-effect level
However:
• The smaller the more toxic (Donaldson et al. 2000)
Riepe, 2003
Grenzwerte: sind gesetzlich verankerte (justiziable) grössen; eine überschreitung ist demnach klagbar;
bei jeder messung treten allerdings messfehler auf (zufällige und systematische fehler); daher gilt das
der grenzwert nur innerhalb eines bestimmten toleranzbereiches gültig ist; wird ein grenzwert
gemessen, so lässt sich nicht genau sagen ob man jetzt schon darüber oder noch unterm grenzwert liegt!
Vorsorge-, richt-, und orientierungs-werte sind nur empfehlungswerte und haben daher keine
gesetzeskraft;
In some fine powders, including ultrafine titanium dioxide, carbon blacks, and fumed silicas, specific surface
areas in excess of 2·E5m2/kg [200m2/g] are achieved among particles with aerodynamic diameters less
than 4 mm. In comparison, an aerosol of spherical particles 4mm in diameter and with unit density
would have a specific surface area of 1.5 x 103m2/kg [1.5m2/g]. There is evidence that for some lowsolubility materials toxic response may be associated with surface area or even particle number
(Oberdorster et al., 1994; Lison et al., 1997; Donaldson et al., 1998).[1]
Donaldson et al. (2000) documented that nano-particles have profound effects upon the recipient tissues.[2]
They found that nano-particles are more inflammogenic than their coarser siblings made of the same
material. The cut-off size for this increased toxicity was found among a gradient that showed the
greatest effect at particles smaller 65 nm and gradually decreased and levelled off towards larger
diameters around 200 nm. The properties that drive this toxicity are still largely unknown.
Nonetheless, it was possible to relate oxidative stress responses of the target cells to particle number
concentration and their associated surface area. In addition, while one kind of nano-particle exerted a
moderate inflammogenic response, the effects increased or even became synergistic when otherwise
harmless nano-aerosols were added to the mono-specific class of particles.
Legally binding threshold values and the corresponding alarm levels for authorities.
General risk assessment chart, assigned to an exposed public (dots represent the individual members)
Source: [1] B.A.Baron & K.Willeke (2001). Aerosol Measurement Principles, Techniques and Applications,
2nd e.d; [1] p.781-782;
[2] Donaldson K., Stone V., Gilmour P.S., Brown D. M., MacNee W. (2000). Ultrafine Particles:
Mechanisms of Lung Injury. Philosophical Transactions: Mathematical, Physical and Engineering
Sciences, Vol. 358, No. 1775, Ultrafine Particles in the Atmosphere, pp.2741-2749.
Intro
Food
Epigenome
Method
Implication
Historic Review
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Intro
Food
Epigenome
Method
Implication
History (1/6)
The Analyst
i)
Society for Analytical Chemistry
(UK, 1874) published its first issue of
ii)
the Analyst in March 1876
Aim: …. the object of THE ANALYST is not only to
present to its readers the latest and best
authenticated processes of analysis …. but to
publish all cases of prosecution for
adulteration, and such parliamentary and
other proceedings as may appear to touch the
interests of Analysts in general.
…. a major step towards a fragmentated
science;
Analyst 1876, 1:1
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p.23: die seinerzeitigen lebensmitt-elexperten witterten im erfindungsreichtum ihre chancen: sie
vermischten besonders begehrte genussmittel mit minderwertigen produkten und liessen sich
diese »streckung« der produkte so bezahlen, als ob sie nicht stattgefunden hätte …. Die erste
wissenschaftliche zeitschrift der »society of public analysts« (1874): »the analyst« (1876)
dienten dem erfahrungsaustausch mit dem ziel, den panschern auf die sprünge zu kommen ….
p.25: Mit der zersplitterung des qualitätsbegriffs in einzelne, untergeordnete merkmale verliert
sich die rechtfertigung, von qualität zu reden, zugunsten einer zweifelhaften angabe über die
zweckmässigkeit …. Solange chemikalien der nahrung zugesetzt werden, erhöht sich das risiko
verminderter qualität, während die verhinderung des zusatzes einzelner stoffe …. die
höchstmengen-verordnung liefert deshalb unbedingt notwendige, aber keineswegs hinreichende
qualitätsleitwerte …. Kurioserweise verdanken wir die »naturbelassenheit« der kost immer
mehr der sorgfalt von lebensmittel-ingenieuren …. Die lebensmittelindustrie geht ….
neuerdings der folgender strategie nach: die in der nahrung natürlich vorhandenen substanzen,
die den genusswert erhöhen, werden angereichert, andere, die die frische günstig beeinflussen,
zugefügt, wieder andere, die den verkauf der ware fördern, gezielt verstärkt oder beigemischt,
jene aber, die nutzlos erscheinen, soweit es geht herausverdünnt …. (Kerbusk 1993).
Dieses unter dem schlagwort »lebensmittel-funktionalitaet« betriebene vorgehen erinnert an
optimierungsprozesse …. warum sollten lebensmittel-chemiker, mit höherem sachverstand
ausgerüstet, diese optimierung nicht noch besser vornehmen können als eine erfahrene, aber
rücksichtslose natur? ….
p.xxi: Schauen sie sich doch mal die forschungslandschaft an. Wenn heute jemand irgendwo als
forscher arbeitet, dann hat er ein spezielles gebiet .... Jeder hat so ein spezialgebiet und 99% der
kollegen wären gar nicht in der lage die ganze problematik zu erfassen die ja von
interdisziplinärer natur ist .... Man darf gar keine fachdisziplin in den vordergund stellen,
sondern muss die fragestellung in den vordergrund rücken.
Source: Kerbusk K.P.1993.Der Gen-Frass. Biotechniker bauen die Nahrung um. Der Spiegel 15,
202-218
http://en.wikipedia.org/wiki/The_Analyst_(chemistry_journal)
http://www.rsc.org/Publishing/Journals/an/Article.asp?Type=CurrentIssue
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Epigenome
Method
Implication
History (2/6)
Rene Descartes (1596 – 1650 )
i)
philosopher, mathematician, scientist, and writer;
ii)
scientific progress via technical means;
iii) rational knowledge: “incapable of
destroyed”; search for truth in science;
being
iv) Discourse on the Method
-
accept only that which you are sure of;
-
Divide into as small parts as necessary;
-
Solve the simplest problems first;
-
Make as complete list as possible;
Wikipedia, 2009
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p.33: …. Der französische mathematiker und filosof Rene Descartes lebte von 1596 bis 1650 ….
Ähnlich widersprüchlich und deshalb vital - bei weitem nicht notwendig falsch - in der
wissenschaft den fortschritt und die technischen mittel für arbeitserleichterung bis hin zur
selbstverwirklichung des menschen zu erkennen. Von ihm geprägt, folgt die wissenschaft ….
Noch heute einigen regeln seiner methode des richtigen vernunftgebrauchs:
- vermeide alle vorurteile und erkenne nur das als wahr an, was sich klar und deutlich nachweisen
lässt,
- zerlege die probleme soweit als möglich in einzelteile,
- schreite vom einfachsten objekt gleichsam stufenweise zum komplizierten voran,
- sichere die vollständigkeit des systems durch aufzählung.
Source: http://en.wikipedia.org/wiki/Descartes
http://en.wikipedia.org/wiki/Discourse_on_Method
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Method
Implication
History (3/6)
…
.b
u
is t R
no en
tr eD
ed e
uc sc
ib ar
le te
to s k
ste new
am t
-e hat
ng a
in hu
e… m
a
. n
Denis Papin (1647 - 1712)
Medical scholar who joined Christian Huygens, who
was working with air pumps …. Together they
pionered the invention of the steam digester, the
forerunner of the steam engine.
Energetic requirements to power the human body:
1. energy supply for internal and external work, to
maintain heartbeat or contraction of muscles;
2. assurance of necessary materials for cell-growth,
3. body heat regulation;
Wikipedia, 2009
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Begonnen aber hat es damit, dass beim abbau aller vorurteile und der beschränkung auf das, was
klar und deutlich nachweisbar ist, der mensch sich scheinbar nicht mehr von einer maschine
unterscheiden lässt. Descartes hätte hier freilich bereits protestiert, denn eine maschine
kann nicht zweifeln ….
p.34: Aber als man die parallelität des menschen mit der dampfmaschine erkannte - im übrigen
lange zeit nach Descartes -, waren die selbstzweifel der wissenschaftler zugunsten der
fortschritts-gläubigkeit ausgeräumt …. der treibstoff (nahrung) für den menschen dient nach
diesem modell den folgenden drei funktionen:
1. der zufuhr notwendiger energie für innere und äussere arbeit, wie herzschlag beziehungsweise
kontraktion der muskeln,
2. der sicherung notwendiger substanzen für das zellwachstum,
3. der wärmeregulation.
p.35: …. Im menschen sterben etwa 1·E6 zellen pro sekunde ab - die sowohl im korrekten
»timing« als auch mit submolekularer präzision genau ausgeglichen werden; und das trotz
eines lückenhaften nahrungsangebots, mit nicht einmal annähernd passenden bausubstraten wie proteine, lipide, enzyme, nukleinsäuren, vitamine - die nötig sind, um die gesamte
substanz jeder fehlenden zelle zu nachzubilden ….
p.36: Wäre die wachstumsrate der zellen z.b. des darms nur geringfuegig erhöht, stürbe der
mensch innerhalb weniger tage an darmverschluss ….
Source: www.kuhf.org/cdprojects/steam/track8.html
http://www.nndb.com/people/558/000096270/
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Method
Implication
History (4/6)
Missmatch b/w Calories & Excercise:
• Energy pathways (an/aerobic)
• Energy contents of carbo-hydrates
sucrose C12H22O11
glucose C6H12O6
starch C6H10O5)n
triglycerides (fat, RCOOCH2CH(-OOCR')CH2-OOCR )
proteins (AA, H2NCHRCOOH )
• daily allowance: 2000 kCal
MedBio, 2008
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»Guter« treibstoff erfüllt diese aufgaben optimal, zeichnet sich dann durch eine hohe
»ernährungsfysiologische« qualität aus.
Um es klarzustellen: dieser standpunkt muss nicht falsch sein. Er könnte sich aber sehr wohl als
unzureichend erweisen ….
Wenn ein 75kg arbeiter einen 50kg zementsack 10m hochtragen will (PE [J] = mgh,
m=75+30kg) …. dann muss er ca. 0.25 g fett verbrennen (1 kCal = 4187 J), oder zirka 1g
proteine, oder ersatzweise 1g kohlehydrate. Die tägliche menge von zirka 2000 kCal, die der
erwachsene benötigt, reicht immerhin aus, um …. vier klein-LKWs mit je rund 65 sack zement
abzuladen und auf den 30m hohen turm zu tragen …. in einem tag (24h) hat er vergleichsweise
nicht mehr geleistet als eine seiner 100W glühbirnen, die er möglicherweise abzuschalten
vergessen hat (PE [J] = VIt, t=24h60min60s).
Source: www.kuhf.org/cdprojects/steam/track8.html
http://www.nndb.com/people/558/000096270/
http://www.medbio.info/Horn/Time%206/muscle_metabolism_march_2007.htm
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Implication
History (5/6)
the missmatch b/w
Calories & Excercise:
• 5kg fat deposits (= 45·E3 kCal !)
• Loss is difficult to achieve via
mechanical work only;
triathlete.com, 2008
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Physics alone can't supply the answer without biology. If we just consider the work done against
gravity it would take a 200 pound bench press to burn 1 food calorie (4187J).
From here the issue comes down to efficiency, how much effort is wasted? (A human can expend
calories in muscle tension without doing any work, saying nothing of our core bio functions that
run all the time).
Using a cardio-machine to measure ones heart rate yields the wattage of ones physical effort.
Once you know that heart rate x leads to wattage y, just multiply the y of your average heartrate
by the length of your workout (measured in seconds) and by 1/4187 to get a vague idea of your
expended calories.
Source: http://www.beginnertriathlete.com/
www.dna.caltech.edu/courses/cns187/references/brain.pdf
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Method
Implication
History (6/6)
the missmatch b/w
Calories & Excercise:
• 5kg fat deposits (= 45·E3 kCal !)
• Loss is difficult to achieve via
mechanical work only;
• Brain uses 20% of total energy
(20W) or 1kCal every 3.5 mins;
• engaging in mental activity
doubles / tripples energetic
requirements!
triathlete.com, 2008
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The consensus is that a resting human brain uses energy at a rate of 20 Watts, that’s 20% of the
overall energy budget of the human body. Hence, 20 W = 20 J/s = 1200 J/min = 28800 J/day,
and with a kCal = 4187 J, one obtains: 4.8 Cal/s = 0.29kCal/min = 17.2 kCal/h = 412.7 kCal/day!
Or in other words, the human brain uses 1 kCal of energy in about 3.5 min without performing
any particular mental task!
…. One could find menu cards in restaurants indicating, in addition to the price, the energy
content of every dish …. Taken literally, this is just absurd. For an adult organism the energy
content is as stationary as the material content. Since any calorie is worth as much as any other
calorie, one cannot see how a mere exchange could help. What then is that precious something
contained in our food which keeps us from death? …. Everything that is going on in Nature
means an increase of the entropy …. What an organism feeds upon is negative entropy.
p.35: erste schlussfolgerung koennte lauten:
- lohnt es sich überhaupt, sein übergewicht ehrlich abzuarbeiten? 5kg zuviel zwingen uns, 6100
sack zement (zirka 93 klein-LKWs) abzuladen und jeden einzelnen sack 30m hochzuschleppen.
Dafür müsste man vier wochen schweren arbeitsurlaub nehmen.
- sollen wir uns nicht lieber freuen darüber, welche enormen arbeitsreserven schon mit einer
spärlichen mahlzeit aufgenommen werden?
- konnte es der sinn der biologischen evolution sein, uns als energiemaschinen zu gestalten, die es
dann noch nicht einmal mit einer einfachen glühbirne aufnehmen können?
Source: http://www.beginnertriathlete.com/
www.dna.caltech.edu/courses/cns187/references/brain.pdf
Schrödinger E. (1948) What is Life? The Physical Aspect of the Living Cell.
Cambridge: University Press.
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Food
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Implication
Production (1/7)
Communicative Dynamics:
Systems relies on matter, energy and
information:
EQM = h·ν0
ERT = m 0c2
dE + dm + dI = 0
(P.Manzelli, 2006)
Energy: the potential for causing change.
Information: a »bit« of information is
definable as a difference that makes a
difference (Bateson) - the content about
Form & Gestalt in a message.
Matter: the physical & objectifyable world.
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Information-Energy-Matter Triad: With the quantum potential, its effect on a particle depends
on its form rather than its magnitude. The effect is the same regardless of the strength of the
wave. The wave may have larger effects even at long distances, for the wave does not carry
energy; it is an information wave with mental & physical properties (see ship travelling on autopilot controlled by satellite: the information contained within the radio waves actually guides
the enormous energy possessed by the ship).
• Matter: is the substance of which physical objects are composed. It constitutes the observable
(objectifyable) universe. According to the theory of relativity there is no distinction between
matter and energy, because matter can be converted to energy, and vice versa.
Source: Madl P., Yip M.; 2007; The Light of Life – Biophotonics; Proceedings of the 6th
Gathering in Biosemiotics 2006, Umweb - Helsinki;
Manzelli P. 2006. Evolution in "Bio–Quantum Physics“; General Science Journal;
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Production (2a/7)
• Agro Revolution (~8kyrs ago)
• Sessile Lifestyle & Population Growth (current)
modified after Cunningham et al,. 2003; AAAS 2000; Bryant et al., 1998;
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The explosive burst of highly developed urban civilizations - after millions of years without a face
– and which spread over the whole world (so far known to them; e.g. Egypt, Sumer & Akkad in
the Hindu valey, Xia dynasty at the HuangHo, the indigene cultures on the american continent
among others) is remarkable. It must have been this development in which humans finally have
left the line of animal ancestors.
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Implication
Production (2b/7)
• Agro Revolution (~8kyrs
ago)
• Sessile Lifestyle &
Population Growth (current)
modified after
Cunningham et al,. 2003; AAAS 2000; Bryant et
al., 1998;
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The agro-revolution made us sessile, thereby enabling communities to establish villages, cities,
and ultimately larger urban aggregations
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Production (3/7)
Liebig‘s Law
Agro-Industrial Eutrophication (since 1840)
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animated, Reid et al., 2005
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Agro-Industry: since the discovery of Liebig’s law (1850), agricultural productivity skyrocketed
– so did the collateral effects of airborne relocation of essential minerals such as phosphorous and
nitrogen.
In 1840 Justus von Liebig proposed that the single factor in shortest supply relative to demand is
the critical determinant in the distribution of that species (be it bacteria, plant, animal, fungi).
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Production (4/7)
Food & Environment:
• excess nitrogen & phosphate
content in water and foods
since the 1950s;
• introduction of toxins into the
food chain after WWII
(e.g. DDT);
• environmental movement
kicked off in the early 1960s;
• industry helped to cope with
famine …. But at what price?
CERPA 2009
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In den 1950er jahren …. spielte das thema »chemie in der nahrung« keine oder nur eine
untergeordnete rolle ….
p.13: Heue aber gibt es kaum noch ein nahrungsmittel, vor dem nicht schon gewarnt worden
wäre, wie fisch, fleisch, innereien, ja selbst brot, gemüse, obst, milch, nudeln, reis, gewürze, eier
…. Der eigentliche kernpunkt …. ist die qualität der nahrung …. überhöhten stickstoff- und
fosfatgehalt
in
den
böden,
im
trinkwasser,
in
den
lebensmitteln,
durch
schädlingsbekämpfungsmittel,
konservierungsstoffe,
reste
von
tierarzneimitteln,
substitutionsstoffe und aufbesserungs-chemikalien, die qualität der nahrung keinen schaden
erleidet ….
p.15: »Die subventionierte naturzerstörung« (1990): »unsere tische sind reichlich gedeckt...
aber der preis dafür ist hoch, wir bezahlen diese fülle mit einer zunehmenden zerstörung von
natur und umwelt .... Das ist langfristig um so folgenschwerer, zumal es immer noch nicht ernst
genommen und sogar durch agrarpolitische massnahmen weiter kräftig gefördert wird ….
p.17: Die verdrängung wilder pflanzen und tierarten (stehen mit den kulturpflanzen in
konkurrenz) ist kein betriebsunfall, sondern das erklärte ziel landwirtschaftlicher bodennutzung
…. Fremdstoffe und rückstände bestimmten die gesundheit und qualität der nahrung weit weniger
als ihre nährstoffe, dann bedeutet das im klartext, dass es immer noch günstiger sei, giftstoffe mit
der nahrung aufzunehmen als zu verhungern ….
p.123: Die aktuelle situation: …. Die moderne industrie hat die hungersnot …. beseitigt. aber bezahlen wir
den heutigen überfluss …. mit einem unbekannten risiko? Chemikalien, die den ertrag der
landwirtschaftlichen produktion in die höhe trieben, hinterlassen friedhofsruhe, verödung, vernichteten nicht
nur die »schädlinge«, sondern auch die vögel am feldrain, bedrohen schon unsere eigene gesundheit mit
latenten spätschäden …. An sich unschädliche und möglichst natürliche stoffe in die nahrungskette zu
bringen oder »genetisch« zu manipulieren erscheint auf den ersten blick elegant …. jedoch ist dass
lebensmittel aber mehr als die summe ihrer anteile ….
Source; http://en.wikipedia.org/wiki/Silent_Spring
Silent Spring is a book written by Rachel Carson and published by Houghton Mifflin in
September 1962. The book is widely credited with helping launch the environmental movement.
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Production (5/7)
Food & Environment:
Biocides used in modern-style ago-industry:
• Inorganic / Organochlorine Insecticides,
• Herbicides,
• Fungicides, etc.
Uptake via
• skin, (dermal applications);
• lungs (inhalation);
• intestinal tract (ingestion );
Kick-Raack., 2004
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Modern food production employs large scale use of biocides that are introduced into the food chain.
Areas of skin have different rates of absorption. Note that area around head absorbs well. Studies with farm applicators have shown
absorption on back of neck. Certainly do not want pesticide contaminated hat etc to remain on head. Scrotum area is most sensitive.
While palm and forearm not most sensitive, they are still where most exposure occurs for mixers/loaders and often applicators. (Lawn
care applicators have exsposure on legs because the walk into their application. So potential for harm depends on sensitivity of the route
of exposure, where exposure actually occurs, how long the exposure occurs, and the toxicity of the product.
Acute Effects: Immediate “poisoning” or harm and are based on LD50 values. Most sensitive route determines Signal Word.
Chronic Effects: Long-term effects from small doses over time. Not necessarily on label. Some information on MSDS (carcinogenicity,
mutagenicity, teratogenicity = birth defects, oncogenicity, liver damage, Reproductive disorders-sperm count, sterility, miscarriage, nerve
damage, allergenic sensitization).
Source: Joanne Kick-Raack, 2004. Pesticide Poisoning Symptoms & Other Health Issues. Pesticide Education Programs, Ohio State Univ.
The EXtension TOXicology NETwork: http://extoxnet.orst.edu/
http://hhs.sbo.hampton.k12.va.us/IB%20AP%20PowerPoints/APES%20pesticides.ppt
Pesticides:
•Algicides: Control algae in lakes, canals, swimming pools, water tanks, and other sites.
•Antifouling agents: Kill or repel organisms that attach to underwater surfaces, such as boat bottoms.
•Antimicrobials Antimicrobials: Kill microorganisms (such as bacteria and viruses).
•Attractants: Attract pests (for example, to lure an insect or rodent to a trap). (However, food is not considered a pesticide when used as
an attractant.)
•Biopesticides: Biopesticides are certain types of pesticides derived from such natural materials as animals, plants, bacteria, and certain
minerals.
•Biocides: Kill microorganisms.
•Disinfectants and sanitizers: Kill or inactivate disease-producing microorganisms on inanimate objects.
•Fungicides: Kill fungi (including blights, mildews, molds, and rusts).
•Fumigants: Produce gas or vapor intended to destroy pests in buildings or soil.
•Biocides: Kill microorganisms.
•Disinfectants and sanitizers: Kill or inactivate disease-producing microorganisms on inanimate objects.
•Fungicides: Kill fungi (including blights, mildews, molds, and rusts).
•Fumigants: Produce gas or vapor intended to destroy pests in buildings or soil.
•Herbicides: Kill weeds and other plants that grow where they are not wanted.
•Insecticides: Kill insects and other arthropods.
•Miticides (also called acaricides): Kill mites that feed on plants and animals.
•Microbial pesticides: Microorgs that kill, inhibit, or out compete pests, including insects or other microorgs.
•Molluscicides: Kill snails and slugs.
•Nematicides: Kill nematodes (microscopic, worm-like organisms that feed on plant roots).
•Ovicides: Kill eggs of insects and mites.
•Pheromones: Biochemicals used to disrupt the mating behavior of insects.
•Repellents: Repel pests, including insects (such as mosquitoes) and birds.
•Rodenticides: Control mice and other rodents.
16
Intro
Food
Epigenome
Method
Implication
Production (6/7)
Food & Environment:
since the 1950s;
(e.g. DDT);
Mahaffy et al., 2000
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17
It is 1948 Paul Muller receives a Nobel Prize for his discovery of the insecticidal properties of
DDT (dichloro-dipheynl-tricholoethane) was first synthesized 1873. But at that time, it was just
another molecule, with no notable qualities.
In 1935, Muller, a researcher at Geigy (Basle, Switzerland), began looking for chemicals that
might help control Colorado potato beetles. In 1939, he announced finding the insecticidal
properties of DDT.
Research on pesticides -- against typhus louse and mosquitoes -- had been underway since 1941
(by the medical branch of OSRD). Disease was no peripheral military issue: 2.5 million had died
of typhus in World War I. Malaria was now a concern especially in the Pacific theater. The
National Research Council had, since 1940, been organizing research among industries and
foundations for an effective mosquito repellant. DDT research in focused on "military"
effectiveness. By Feb 1943, DDT was shown to be one hundred times more toxic to mosquito
larvae than any alternative. "In October of 1943 a heavy outbreak of typhus occurred in Naples
and the customary relief measures proved totally inadequate. General Fox thereupon introduced
DDT treatment with total exclusion of the old, slow methods of treatment. As a result, 1,300,000
people were treated in January 1944 and in a period of three weeks the typhus epidemic was
completely mastered …. DDT … proved to be extremely valuable in the “fight” against malaria,
this the most widespread of all contagious diseases which yearly affects about 300,000,000 people
with a death rate of 1%.
Source: http://www.tc.umn.edu/~allch001/1815/pestcide/sim/background.htm
http://www.fws.gov/Pacific/ecoservices/envicon/pim/reports/Olympia/HoodCanalEagle.htm
17
Intro
Food
Epigenome
Method
Implication
Production (7a/7)
Food & Environment:
since the 1950s;
(e.g. DDT);
• Endocrine Disruptors (ECD);
Keith, 1997
15-08-21
Madl
Florida alligators: pesticide spill in
Lake Apopka in 1980
• ‘feminized’ males;
• birth rates crashed;
• population declined;
18
Endocrine Disruptors (ECDs): The physiological processes of the endocrine (hormonal) system
can be disrupted by a number of artificially and naturally occurring chemicals. These compounds
may potentially cause adverse effects on human health and wildlife by interfering with the
function of endogenous hormones in the body (Kim et al.). The endocrine system include the
pituitary, thyroid, adrenal glands, and the male and female reproductive systems, all of which
release hormones into the bloodstream. In particular the sex hormones include estrogens in
females and androgens in males. EDCs consist of synthetic and natural chemicals (Persistant
Organic Pollutants, POP) that affect the balance of normal hormonal functions in animals.
Depending on their activity they may be characterized as estrogen modulators or androgen
modulators. They may mimic the sex hormones estrogen or androgen, thereby producing similar
responses to them or they may block the activities of estrogen or androgen; i.e. anti-estrogens or
anti-androgens (Keith, 1997).
Source: Keith L.H. (1997). Environmental endocrine disruptors – A handbook of properties, John
Wiley & Sons, Inc., New York - USA.
Kim T.UK., Lee H.J., Lee S.Y., Cho J.W., Moon S.H. 2005. A Study on Analysis of EDCs by
Mass Spectrometry and Removal of EDCs by Membranes. A UNU Pilot Programmme on Science
and Technology for Sustainability.
http://en.wikipedia.org/wiki/Lake_Apopka
http://www.epa.gov/endocrine/
18
Intro
Food
Food
Method
Implication
Production (7b/7)
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19
Unwanted Medications:
•
Don’t flush down toilets / drains
•
Properly dispose / recycle
•
Prudent usage
Source: http://www.epa.gov/nerlesd1/chemistry/pharma/image/drawing.pdf
Daughton C. 2004. Pharmaceuticals and Personal Care Products (PPCPs) as Environmental
Pollutants. Environmental Sciences Division. National Exposure Research Laboratory. U.S.
Environmental Protection Agency.
19
Intro
Food
Epigenome
Method
Implication
Production (7b/7)
Food & Environment:
Estimated Chemicals in use (1990)
• chemicals in commerce: 100·E3
• industrial chemicals 72·E3
• annual increase (new): 2·E3
• pesticides: 600
• food additives: 8.7·E3
• cosmetic ingredients.: 7.5·E3
• human pharmaceuticals: 3.3·E3
Keith, 1997
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20
Environmental toxicology: science that examines the effects of poisonous chemicals and other
agents on human and wildlife health.
Toxicology is increasingly important:
* production have expanded the number of new chemicals;
* concentration of chemical contaminants in the environment have increased;
but artificially produced chemicals give us the standard of living we enjoy today;
* industrial agriculture;
* medical advances;
* modern materials and conveniences;
Thousands of synthetic chemicals are toxicants that affect the health of wildlife and people; they
are ubiquitous in the environment and can end up far from their source. Pesticides used to kill
insects and weeds are some of the most widespread and toxic synthetic chemicals (e.g. source:
lawns, farmlands, golf courses). Increased concern about environmental quality; deal specifically
with those toxicants that come from or are discharged into the environment; e.g. Tyrone Hayes of
University of California; illustrate battles where stakes are high, both in economics and human
health; wasn't until 1960s that people began to learn about the risks of exposure to many synthetic
pesticides.
The key event was the publication of Rachel Carson's 1962 book, Silent Spring (DDT)
Source: http://web.bryant.edu/~dlm1/sc372/readings/toxicology/toxicology.htm
20
Intro
Food
Epigenome
Method
Implication
Production (7c/7)
Food & Environment:
Estimated Chemicals in use (1990)
• chemicals in commerce: 100·E3
• industrial chemicals 72·E3
• annual increase (new): 2·E3
• pesticides: 600
• food additives: 8.7·E3
• cosmetic ingredients.: 7.5·E3
• human pharmaceuticals: 3.3·E3
e.g. Hg-exposure
Stenstrup , 2003
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21
Above is a schematic drawing of mercury cycling in an aquatic ecosystem. With the exception of
isolated cases of known point sources, the source of most mercury to most aquatic ecosystems is
deposition from the atmosphere, primarily associated with rainfall.
Source: http://www.mercuryinschools.uwex.edu/curriculum/hg_in_env.htm
http://www.mercuryinschools.uwex.edu/project/index.htm
21
Intro
Food
Epigenome
Method
Implication
Distribution (1/1)
Food Distribution - Globalization
• globalization boosted focus on
monetary value of production;
• is reflected in the shift from bulk
commodities towards processed
foods;
• encompasses organic foods as well;
Regmi & Gehlhar, 2001, 2006
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22
Area devoted to pear growing areas has increased sharply in Chile in the last 12 years, reaching in
1995 about 17.500 hectares (compared to 6.600 ha in 1985). Cultivation of this crop in Chile
extends between the latitude 32° and 35° South, corresponding to Metropolitana, VIth and VIIth
Regions. The main cultivated varieties are Packham's Triumph (37.4%), Beurré Bosc (23.7%),
Anjou (4.9%) and Red Sensation (11.4%). The main problems in this specie are: inadequate
zonification of varieties and lack of precocity in most of them. The profitability of the cultivation
has been, however, seriously impacted by the increase of the volume produced and low fruit sales
prices, obtaining returns between US$ 2.8–3.0 per box for the grower (this mean 17% of the final
sales price at the port). The export volumes have surpassed 9 million boxes. The main Chilean
pears importers are North America (25.0%) and Europe (25.5%).
20 yrs ago, bulk commodities that consisted primarily of grains and oilseeds accounted
for most agricultural trade; however, in recent years processed and semi-processed
products have jointly accounted for 2/3 of total agricultural trade. Highvalue food products
are nonbulk commodities that either require special handling, such as fresh produce, or
are processed, which adds substantial value beyond the farm level. Processed foods are
edible foodstuffs that have been transformed from their original post-harvest states to
either semi-processed products (flour and meal) or final products (bread and breakfast
cereal).
Image: U.S. Bulk Commodities Export Share Dropped About 30 Percent During 1980-98
Source: Regmi A., Gehlhar M., 2001. Global Food Trade - Consumer Preferences and Concerns.
Food Review. Vol. 24 (3): 2-8;
Yuri, J.A. and Torres, C. 1998. PEAR PRODUCTION IN CHILE: GROWING AREAS,
CULTIVARS, EXPORTS AND PROFITABILITY. Acta Hort. (ISHS); 475:27-34
(http://www.actahort.org/books/475/475_1.htm)
22
Intro
Food
Epigenome
Method
Implication
Processing (1/8)
Food Additives - E-numbers
• number codes for food additives;
• on food labels throughout the EU;
Two examples
i) Conservants
i) Packaging
i) Radiation
i) GMO
INDIAWO, 2006
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23
Genuss ohne qualität: Seit gut 2000 jahren streiten die filosofen darüber, ob der wahre genuss
darin besteht, ihn voll auszuschöpfen (hedonismus) oder auf ihn gänzlich zu verzichten (askese).
Bis heute hat sich diese schaukelei zwischen schweinsbraten und fastenkur erhalten, ja sogar zu
einer neuen genialen variante entfaltet, wobei der geschmack der lebensmittel mit
verstärkersubstanzen, aromastoffen, färb- und konsistenzmitteln bis hin zu psychofarmaka
»vollendet« oder ersetzt wurde. Der verbraucher weiss nicht mehr, ob er der völlerei verfallen ist
oder in wirklichkeit zu den asketen gehört.
Die industrie bedenkt sehr wohl auch die bedürfnisse des kunden, denn ziel ist es,
- die »natürliche« frische soweit wie möglich zu erhalten,
- den »natürlichen« geschmack täuschend ähnlich nachzuahmen oder gar zu übertreffen,
- den »natürlichen« geruch auch dann noch aufrechtzuerhalten, wenn das system »lebensmittel«
unter natürlichen bedingungen schon längst verfault und von verwesung befallen wäre,
- das aussehen so appetitlich wie möglich zu gestalten, so dass man am liebsten sofort zubeissen
möchte und es kaum noch ab warten kann ....
Source: www.ksoe.ch/lernangebot/indiawo06/
23
Intro
Food
Epigenome
Method
Implication
Processing (2/8)
Food Additives – Conserving Life:
Consequences of improper processing,
“western” diet & medical overdose:
… we ….
• consume over 3kg of chemicals/year;
• live longer;
• die slower;
• become older – the older we are,
the more “conserved” we become;
Engel, 2004 & wikipedia, 2009,
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24
p.xl: Die moderne westliche esskultur bringt uns um. Wir leben zwar länger, aber im grunde genommen
leben wir nicht länger sondern wir werden konserviert. Wir sterben langsamer ....
p.79: As if this is not bad enough, further strain is placed on the body by the assortment of
chemicals needed to preserve colour, dry, flavour and tenderise processed food, in order to get
people to eat it. By this stage, it is not really food but more a composition of reconstituted,
chemical-laden organic matter. A recent study has shown that the average person now consumes
about three kilograms of chemicals per year, in the form of food additives. The human body was
never designed to be so constantly abused. It becomes overloaded and develops allergies to all the
unnatural rubbish with which it has been constantly fed. It is again a matter of degree. A little
processed food, now and again, is no problem for a healthy body. But, when it is eaten on a daily
basis, year after year, as the main ingredients of the diet, the body will lose its capacity to cope,
and an insidious form of ill health will result.
Source: http://en.wikipedia.org/wiki/Parkinson%27s_disease
Engel C.C. 2004. Stepwise Care for The Recently Deployed and Their Families - A Populationbased Model of Care.
Uniformed Services University, Walter Reed Army Medical Center.
Griffiths S. 1996. Allergy overload. HarperCollins (Australia)
24
24
Intro
Food
Epigenome
Method
Implication
Processing (3/8)
E100–E199 (colours)
E200–E299 (preservatives)
E300–E399 (antioxidants, acidity regulators)
E400–E499 (thickeners, stabilizers, emulsifiers)
E500–E599 (acidity regs, anti-caking agents)
E600–E699 (flavour enhancers)
E700–E799 (antibiotics)
E900–E999 (miscellaneous)
E1000–E1999 (additional chemicals)
zusatzstoffe-online.de, 2009
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25
Konservierungsstoffe sind zusatzstoff-stoffe, die die haltbarkeit von lebensmitteln verlängern,
indem sie diese vor den schädlichen auswirkungen von mikroorganismen schützen. Sie müssen
zugelassen werden und dürfen nur für bestimmte lebensmittel und in begrenzter dosierung
verwendet werden; z.b. die schalen von orangen ist häufig mit wachsen behandelt, denen (außer
im Ökolandbau) meist konservierungsstoffe zugesetzt werden (generell bedenklich da 12mg/kg
koerpergewicht nicht ueberschritten werden duerfen):
i) Thiabendazol (E 233),
i) Orthofenylfenol (E 231),
i) Natriumorthofenylfenol (E 232),
i) Bifenyl (=Difenyl) (E 230) und
i) Imazalil (0,03 mg/kg/tag)
Wegen ihrer pilzabtötenden wirkung sind sie ausschliesslich für die oberflächen-behandlung von
zitrusfrüchten zugelassen. Die konservierungsstoffe werden entweder direkt auf die schale der
früchte aufgebracht oder im falle von bifenyl auch indirekt durch einwickelpapier, kartons oder
zwischeneinlagen. Auch das fungizid thiabendazol (E 233) wird u.a. für die haltbarmachung von
zitrusfrüchten eingesetzt und ist in verwendung und wirkungsweise in diesem fall mit einem
konservierungsstoff vergleichbar.
Source: http://www.landwirtschaft-mlr.baden-wuerttemberg.de/servlet/PB/menu/1104695_l1/index.html
25
Intro
Food
Epigenome
Method
Implication
Processing (4/8)
E100–E199 (colours)
E200–E299 (preservatives)
E300–E399 (antioxidants, acidity regulators)
E400–E499 (thickeners, stabilizers, emulsifiers)
E500–E599 (acidity regs, anti-caking agents)
E600–E699 (flavour enhancers)
E700–E799 (antibiotics)
E900–E999 (miscellaneous)
E1000–E1999 (additional chemicals)
zusatzstoffe-online.de, 2009
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26
p.31: …. Unfair erscheint aber schon, dass man als normalverbraucher heute mehr und mehr
gezwungen ist, mit dem biochemie-lexikon oder der auflistung der basensequenzen der
chromosomen unter dem arm einzukaufen, um sich richtig zu ernähren ….
Wir müssen klarheit schaffen darüber, was wir eigentlich wollen ….
Deshalb ist es notwendig, objektive und ganzheitliche massstäbe für die nahrungsqualität zu
finden, die uns erklären können,
- worin der unterschied zwischen einem natürlich frischen salat und dem auf künstliche weise
frisch erhaltenen salat besteht,
- welche konsequenzen die manipulation der natürlichen haltbarkeit, des natürlichen aussehens,
der farbe und der sensorischen eigenschaften, wie geruch und geschmack, nach sich ziehen.
Notwendig dafür ist es, nicht nur zu wissen, was lebensmittel sind, sondern vor allem, was
»leben« selbst bedeutet.
Source: http://www.zusatzstoffe-online.de/home/
http://www.minutella.ch/e/index.htm
26
Intro
Food
Epigenome
Method
Implication
Processing (5/8)
Food Additives - Packaging
D
(0 ie
0:
31 A
:0 k
5 te
–
00 A
:3 lu
2:
10
)
• Aluminium
i) Al as wrappers & containers
i) Al-chlorohydrate: AlnCl(3n-m)(OH)m
used in deodorants & antiperspirants
i) as coagulant in water purification.
i) Al-hydroxide, Al(OH)3 to induce
inflammation in vaccines
• see slide 43 ff
Wikipedia, 2009
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Madl
27
•Al-chlorohydrate-salt: AlnCl(3n-m)(OH)m is used in deodorants & antiperspirants and as a coagulant in water
purification.
•Al-hydroxide, Al(OH)3, (hydroxoaluminate: Al(OH)4− anion @ pH>8 of Al(OH)3
Timelog: dieaktealuminium.files.wordpress.com/2013/04/pressemappe.pdf
‎
19:04: Philippa Dabre - investigations of toxic potential of minute traces of aluminium in antitranspirant comparative studies with women who suffer breast
cancer and those who do not, higher traces of Al have been found in breast-liquids women who had breast cancer
21:05: breast cells degenerating into tumor cells when in contact w/ Al
http://www.sciencedirect.com/science/article/pii/S0162013405001613
Darbre PD. (2005). Aluminium, antiperspirants and breast cancer. J.o.Inorg Biochem. Vol.99(9):1912-1919.
21:35: Al promotes transmigration across cells & formation of metastasis
23:27: 2/3 of all anti-transpirants contain Al-compounds - Al reacts w/ skins cells & blocks cysts - sweat doesn‘t form 23:50: pure Al does not exist .... Al occurs
only in its oxidated form; e.g. bauxite @ Porta Trompetas
27:25: bauxite results from the weathering of Al-rich ores. 250 soccer fields/year of pristine tropical rainforest sacrifieced
31:05: commercial to promote the use of Al-products
32:15: University of Vienna - allergy trigger (asthma, seasonal rhinitis, neuro-dermitis, etc.) Isabella Pali-Schoell & Erika Jensen Jarolim: Al-hydroxide (AlOH) used to induce
allergic reaction to boost immunisation response of vaccines; AlOH used to moderate pH during heart burn (sodbrennen); inducing allergic response in mice by feeding
apples together with Al-hydroxide
34:30 kids are more likely to become allergic when mothers took Al-containig medicine during pregnancy (epigenetics) e.g. heart burn medication during pregnancy
35:40: Herwig Holzer - neurological disorders, speech problems, stroke-like symptoms in young individuals, Alzheimer-like symptoms have been observed in
patients that underwent dialysis, these patients have been given Al-containing medications …. See Wawschinek O., Petek W., Lang J, Pogglitsch H, Holzer H (1982)
The determination of aluminium in human plasma. Microchim. Acta, Vol.77(5-6): 335-339 http://link.springer.com/article/10.1007/BF01197113#
42.10: Al is the only compound in nature that is not used in organismic metabolism or may serve for a specific functions
Christoopher Exley http://www.keele.ac.uk/aluminium/groupmembers/chrisexley/
Darbre PD, Mannello F and Exley C (2013) Aluminium and breast cancer: Sources of exposure, tissue measurements and mechanisms of toxicological actions on breast
biology. Journal of Inorganic Biochemistry 128, 257-261. http://www.sciencedirect.com/science/article/pii/S0162013413001608
Minshall C, Nadal J and Exley C (2014) Aluminium in human sweat. Journal of Trace Elements in Medicine and Biology 28, 87-88.
http://www.sciencedirect.com/science/article/pii/S0946672X13001612
Exley (2013). Human exposure to aluminium. Environ.Scie.Proc.& Impacts.15:1807-1816.http://pubs.rsc.org/en/Content/ArticleLanding/2013/EM/c3em00374d#!divAbstract
House E, Polwart A, Darbre P, Barr L, Metaxas G, Exley C (2013) The aluminium content of breast tissue taken from women with breast cancer.
Journal of Trace Elements in Medicine and Biology. 27, 257-266. http://www.sciencedirect.com/science/article/pii/S0946672X13000576
Chuchu N, Patel B, Sebastian B, Exley C (2013). The aluminium content of infant formulas remains too high. BMC Pediatrics. 13:162
http://www.biomedcentral.com/1471-2431/13/162
48:00 reddish NaOH-enriched sludge as far as the eye can see
48:30 http://en.wikipedia.org/wiki/Aluminium_hydroxide Al(OH)3
for the cosmetic & pharmaceutical industry, too boost immunological reaction
51:50 workers affected by Al-exposure .... brittle bones, sleeplessness, headaches, acid-burnt skin,
56:20 locals using the water on a daily basis .... skin ruptures, skin itches, water burns like pepper ..... dam ruptured and flooded land where locals live, dust contaminated their fields
59:10: http://wwf.panda.org/wwf_news/press_releases/special_coverage/hungary_mud_sludge_toxic_red/
1:05:00: molten Al-meets water from the sprinkler during the collapse of the twin-tower in NY; Boing: 82,3t (Al-share: 30t) Christian Simensen:
Al+H2O at 800C -> Al2 (OH) 3 + H2
http://www.sintef.no/home/Press-Room/Research-News/New-theory-explains-collapse-of-Twin-Towers/
1:07.00 solid rocket boosters use Al-compounds as rocket fuel
1:10:00 Camelford (UK): using Al-compounds to cleanse water - dead fish, bluish water, odd taste .... flushing the drinking water pipeline. Al-sulfate has been erroneously into the
wrong pipe people suffered from rheumatic, 10 out of 40 sheep who drank of it died, neurologial disfunction among several members of the village.
Exley found traces of Al in deceased 1.2ug/g brain mass in most adults in Alzheimer patients even 4-6ug/g and 23ug/g in deceased victims of Camelford
1:19:00 Ruhrgebiert uses AlCl3 to cleanse water
1:20:20: Paris likewise .... there remains always a rest of Al-traces in the water; Andre Picot induces shift to Fe-oxide powder
1:22:30 Alzheimer patients
1:24:00 Exley claims that Al is a neurotoxin
1:28:26 Romain Gherardi macrophages filled with Al-particles introduced into vaccines redistributed throughout the body, i/o lymphatic system and into the CNS
Al-hydroxide is used in vaccines since 1927; in some individuals it is never excreted;
Gherardi RK, Coquet M, Cherin P, Belec L, Moretto P, Dreyfus PA, Pellissier JF, Chariot P, Authier FJ. Macrophagic myofasciitis lesions assess long-term persistence of
vaccine-derived aluminium hydroxide in muscle. Brain. 2001 Sep;124(Pt 9):1821-31. http://brain.oxfordjournals.org/content/124/9/1821.long
1:31.30: 8th int. congress on autoimmunity 2012, Granada Spain). Yehuda Shoenfeld on the topic of Al-hydroxide and Mg-carbonate .... Al-particles can penetrate i/o the brain
congress conclusion: pharmaceutical companies are urged to invest in Al-free vaccines
1:33:00 EU does not see the potential danger of it
Shaw CA, Tomljenovic L. (2013) Aluminum in the central nervous system (CNS): Toxicity in humans and animals, vaccine adjuvants, and autoimmunity.
Immunol Res. 2013 Jul;56(2-3):304-16. doi: 10.1007/s12026-013-8403-1. http://link.springer.com/article/10.1007%2Fs12026-013-8403-1
Tomljenovic L. (2011). Aluminum and Alzheimer's disease: after a century of controversy, is there a plausible link? J Alzheimers Dis. 2011;23(4):567-98. doi: 10.3233/JAD-2010101494. http://iospress.metapress.com/content/vq1p78553222661m/?genre=article&issn=1387-2877&volume=23&issue=4&spage=567
Source: http://en.wikipedia.org/wiki/
27
Intro
Food
Epigenome
Method
Implication
Processing (6a/8)
nt
im Pl
o n as
(1 tic
:0
1: E
00 ra
–1
:0
3:
2
…. Acetaldehyde-formation
CH3CHO
…. a question of dosage
(determines toxicity)
3)
• PolyEthylene Terephthalate;
A
Wikipedia, 2009
15-08-21
Madl
28
PolyEthylene Terephthalate (PET, PETE, or the obsolete PETP or PET-P), is a thermoplastic
polymer of the polyester family and is used in synthetic fibers; beverage, food and other liquid
containers. PET consists of polymerized units of the monomer ethylene terephthalate, with
repeating C10H8O4 units. It contains the chemical elements carbon, hydrogen, and oxygen. If fully
burned, it produces only carbon dioxide (CO2) and water (H2O). PET is commonly recycled, and
has the number "1" as its recycling symbol.
PET degradation: formation of acetaldehyde …. It is a colorless liquid with a fruity smell. When
acetaldehyde is produced, some of it remains dissolved in the walls of a container and then
diffuses into the product stored inside, altering the taste and aroma. This is not such a problem for
non-consumables such as shampoo, for fruit juices, which already contain acetaldehyde or for
strong-tasting drinks, such as soft drinks. For bottled water, low acetaldehyde content is quite
important, because if nothing masks the aroma, even extremely low concentrations can be tasted
(10-20 parts per billion parts of resin, by weight).
Acetaldehyde (ethanal) is an organic chemical compound with the formula CH3CHO or MeCHO.
Acetaldehyde occurs naturally in ripe fruit, coffee, and fresh bread, and is produced by plants as
part of their normal metabolism. It is popularly known as a chemical that causes hangovers ….
Most people of East Asian descent have a “mutation” in their alcohol dehydrogenase gene that
makes this enzyme unusually effective at converting ethanol to acetaldehyde, and about half of
such people also have a form of acetaldehyde dehydrogenase that is less effective at converting it
to acetic acid. This combination causes them to suffer from the alcohol flush reaction, in which
acetaldehyde accumulates after drinking, leading to severe and immediate hangover symptoms.
Acetaldehyde is toxic when applied externally for prolonged periods, an irritant, and a probable
carcinogen. In addition, acetaldehyde is damaging to DNA and causes abnormal muscle
development as it binds to proteins.
Source: http://en.wikipedia.org/wiki/PET_bottle
http://en.wikipedia.org/wiki/Acetaldehyde
28
Intro
Food
Epigenome
Method
Implication
So tre
to
(1 po
:2 is
8: o
00 n
–1 q
:3 uo
2:
23 tid
)
i
en
Processing (6b/8)
Mammary gland of unborn mouse: untreated
15-08-21
vs. 250ng/kg treated
Madl
:N
A
na
id
eo
Wikipedia, 2009
V
• Bisphenol A (BPA);
…. Endocrine disrupting activity
C15H16O2
o
Sonnenschein & Soto, 2010
29
There are seven classes of plastics used in packaging applications. Type 7 is the catch-all "other"
class, and some type 7 plastics, such as polycarbonate (sometimes identified with the letters "PC"
near the recycling symbol) and epoxy resins, are made from BPA monomer. When such plastics
are exposed to hot liquids, BPA leaches out 55 times faster than it does under normal conditions,
at up to 32 ng/hour (boiling for an hour: 29 parts per trillion) Type 3 (PVC) can also contain BPA
as antioxidant in plasticizers. Types 1 (PET), 2 (HDPE), 4 (LDPE), 5 (polypropylene), and 6
(polystyrene) do not use BPA.[1]
Bisphenol A (BPA), is an organic compound with two phenol functional groups. It is an important plastics and plastic
additives. BPA has low acute toxicity, with an oral LD50 of 3250 mg/kg in rats, but it is an endocrine disruptor. Low doses
of BPA can mimic the body's own hormones, possibly causing negative health effects. There is thus concern that long term
low dose exposure to BPA may induce chronic toxicity in humans.
0.025
"Permanent changes to genital tract”
0.025
"Changes in breast tissue that predispose cells to hormones and carcinogens”
2
"increased prostate weight 30%”
2
“< bodyweight, >anogenital distance in both genders, early puberty and longer estrus.”
2.4
"Decline in testicular testosterone”
2.5
"Breast cells predisposed to cancer”
10
"Prostate cells more sensitive to hormones and cancer”
10
"Decreased maternal behaviors”
30
"Reversed the normal sex differences in brain structure and behavior”
50
U.S. human exposure limit (not a result from an animal study, but a guideline set by EPA);
Lang and colleagues found that high BPA levels were significantly associated with heart disease,
diabetes, and abnormally high levels of certain liver enzymes. [2]
Perinatal exposure to low-doses of bisphenol-A (BPA) results in alterations in the ovary, uterus,
and mammary glands and in a sexually dimorphic region of the brain known to be important for
estrous cyclicity.[3]
Source: http://en.wikipedia.org/wiki/Acetaldehyde
[1] Saal F.S., Myers J.P., 2008. Bisphenol A and Risk of Metabolic Disorders. JAMA. 2008;300(11):1353-1355.
Lang I.A., Galloway T.S., Scarlett A., Henley W.E., Depledge M., Wallace R.B., Melzer D. 2008. Association of Urinary
[2]Bisphenol A Concentration With Medical Disorders and Laboratory Abnormalities in Adults. JAMA.
2008;300(11):1303-1310
[3] Cabaton N.J., Wadia P.R., Rubin B.S., Zalko D., Schaeberle C.M., Askenase M.H., Gadbois J.N., Tharp A.P., Whitt
G.S., Sonnenschein C., Soto A.M. 2010. Perinatal Exposure to Environmentally Relevant Levels of Bisphenol-A
Decreases Fertility and Fecundity in CD-1 Mice. Environmental Health Perspectives. doi: 10.1289/ehp.1002559
29
Intro
Food
Epigenome
Method
Implication
Processing (7a/8)
Food Additives - Radiation
• Radura-logo …. indicates that a food
has been treated with ionizing radiation;
Food irradiation can - mask spoiled food,
Wikipedia, 2009
- discourage to good manufacturing practices,
- kill 'good‘ / encourage growth of 'bad' bacteria,
- devitalise and denature irradiated food,
- impair the flavour,
- not destroy bacterial toxins already present,
- cause harmful chemical changes,
- unnecessary in today's food system.
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Die lebensmittel-bestrahlung verfolgt eine reihe von zielen, die durch unterschiedlich hohe
bestrahlungsdosen erreicht werden: a) hemmung der keimung und der reifung; b) bekämpfung
von insekten und parasiten; c) erhöhung der haltbarkeit; d) eliminierung von mikroorganismen;
e) sterilisierung;
Die wirkung der bestrahlung beruht auf der zerstörung des genoms und damit der fortpflanzungsund ueberlebensfähigkeit der bestrahlten organismen. Aufgrund ihrer grösse ist die DNA
bedeutend stärker empfindlich gegenüber ionisierenden strahlen als kleinere molekül. Zur
verwendung kommen elektronenstrahlung und bremsstrahlung (röntgenstrahlung) aus
teilchenbeschleunigern sowie gammastrahlen aus dem zerfall von 60Cobalt oder 137Cäsium. Die
energie der fotonenstrahlung von 60Co (1,12 & 1,33 MeV) und von 137Cs (0,66 MeV) ist zu
gering, um eine kernaktivierung auszulösen (radioaktiver zerfall). Seitens internationaler gremien
(FAO, IAEA und WHO) wurde bestätigt, dass lebensmittel jeglicher art bis zu einer ‚mittleren
scwellwert-dosis‘ von 10 kGy ohne bedenken bestrahlt werden können (Gray: ist der quotient aus
der aufgenommenen energie und der masse des körpers. 1 Gy = 1 J/kg = 100 rd).
Low Dose Applications (up to 1 kGy)
* Sprout inhibition in bulbs and tubers 0.03-0.15 kGy
* Delay in fruit ripening 0.25-0.75 kGy
* Insect disinfestation (quarantine) elimination of food borne parasites 0.07-1.00 kGy
Medium Dose Applications (1 kGy to 10 kGy)
* Red. of spoilage microbes to prolong shelf-life (meat, poultry & frozen seafoods 1.50–3.00 kGy
* Red.of pathogenic microbes in fresh and frozen meat, poultry & seafoods 3.00–7.00 kGy
* Reducing the number of microorganisms in spices to improve hygienic quality 10.00 kGy
High Dose Applications (above 10 kGy)
* Sterilisation of packaged meat, poultry &their products which are shelf stable w/o refrigeration. 25.00-70.00 kGy
* Sterilisation of Hospital diets 25.00-70.00 kGy
* Product improvement as increased juice yield or improved re-hydration
It is important to note that these doses are above those currently permitted for these food items by the FDA and other
regulators around the world. The Codex Alimentarius Standard on Irradiated Food does not specify any upper dose limit.
NASA is authorized to sterilize frozen meat for astronauts at doses of 44 kGy as a notable exception.
Source: http://en.wikipedia.org/wiki/Food_irradiation
http://de.wikipedia.org/wiki/Lebensmittelbestrahlung
30
Intro
Food
Epigenome
Method
Implication
Processing (7b/8)
Community Science
Action Guides, 2009
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31
Food Irradiation: After the World War II, scientists looked for new ways to improve life
utilizing applications of nuclear energy. One of these applications is that of food irradiation. This
process is used to kill dangerous diseases associated with foods. The first use of food irradiation
was used during the early 60's, this technique was applied to foods such as wheat, flour, and
potatoes. As population grew, the need for new solutions for "cleaning food" also grew. So in the
early 80's people started using food irradiation on spices, seasonings, fruits, vegetables and for
meat such as pork to prevent trichinosis. Irradiation has become very popular among the growing
community today. Today, over 40 nations have accepted the use of food irradiation. These
countries include China, France, Germany, Great Britain, Israel, Japan, the Netherlands, South
Africa, and the United States among others.
Process: The process of food irradiation is to exposes food to gamma rays from radioactive 60Co.
Food is passed through a small machine where 60Co is located. The food is exposed to the
radioactive material for approximate 15 to 45 minutes depending on the type of food. The food is
packaged before being introduced to the irradiator so the food does not contact other types of
bacteria after being irradiated. When the process is completed, the rods of 60Co are retracted into
a pool of water, which acts as a radiation barrier. This process has been used not only for food but
also to sterilize medical devices, bandages, condoms, tampons, contact lens solution, and food for
astronauts. Irradiation is used to extend the life period of food. This is advantageous in areas
where food refrigeration is not available. The purpose of food irradiation is to clean food in the
very best way possible. The radiation penetrates all parts of the food, killing harmful bacteria that
cause diseases, such as salmonella in seafood, trichinosis in pork, and cholera from fish.
Source: fi.edu/guide/wester/applications.html
31
Intro
Food
Epigenome
Method
Implication
Processing (8a/8)
Food Alteration - GMO:
Genetically Modified Organisms (GMO) ….
• to generate pest-resistant strains (gene-gun);
• acc. to Epigenetics, genes play a subordinate,
role, hence gene manipulation is hit-or-miss
production of potential monstrosities (environmental incompatibility);
• Many GM-DNAs are combinations of genes and genetic material that have
never existed …. risk unknown ….
• but are released into our environment and into the food chain and may be
more invasive to natural habitats than their conventional counterparts;
• GMO-foods: corn, tomato, potato, cotton, squash, papaya, rice, canola,
Walker 2005
sugar beet, flax, soy, radish, cantaloupe, bananas, etc.;
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Advocates of genetic engineering claim that it is no different from what evolution has done, and
that it is in fact a new form of evolution. But genetically engineered crops are not analogous to
products of normal evolution. If epigenetic causation is the motor of evolution as proposed, and
genes play a subordinate, consolidating role, then going at the properties of an organism by
manipulating its genes is not even really “engineering.” It is the hit-or-miss production of
potentially useful monstrosities.
This sharing of genetic information is not an accident. It is nature's method of enhancing the
survival of the biosphere. As discussed earlier, genes are physical memories of an organism’s
learned experiences. The recently recognized exchange of genes among individuals disperses
those memories, thereby influencing the survival of all organisms that make up the community of
life (GMO - shifting the nodes w/n the web of life).
Source: Walker C., 2005: Epigenetics vs. Genetic Determinism - An Interview with Stuart
Newman; Wild Duck Review, Vol.V, (2)
Lipton B. (2005). Biology of Belief. Elite Books p.45
http://en.wikipedia.org/wiki/GMO_food
32
Intro
Food
Epigenome
Method
Implication
Processing (8b/8)
Food Alteration - GMO:
Genetically Modified Organisms (GMO) ….
• are illegitimate recombinations (DNA-scrambling): unspecific DNA-insertion
(distinguishes GM from conventional methods) - not analogous to products
of normal evolution;
• horizontal gene transfer: GM-DNA fragments cross species boundaries;
• ‘Growthfactor-like’ effects in the stomach and intestinal lining of young rats
fed on GM-potato for just 10 days;
• Horizontal transfer of GM-DNA to bacteria in the soil and into human gut has
been found;
• GM DNA of Lactobacillus in heat-treated fermented sausage could still be
detected after 9 months of storage;
I-SIS 2003
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33
Making a GM plant or animal involves breaking and joining the DNA of the host
genome at many unspecifiable locations, a process referred to as "illegitimate
recombination", which distinguishes GM from all conventional methods. This
process leads to substantial scrambling of both foreign and host DNA at the sites
of integration.
….
Topping the list of the direct evidence of hazard inherent to the technology is the
study of Pusztai and co‐workers, who found dramatic ‘growthfactor-like’ effects
in the stomach and intestinal lining of young rats fed GM potato for just 10 days,
which were not present either in rats fed non‐GM potatoes or in rats fed non‐GM
potatoes spiked with the transgene product.
Source: http://www.i-sis.org.uk/GMSRDF.php
THE GM SCIENCE REVIEW PANEL (2003) FIRST REPORT. An open review of the science relevant to GM crops and
food based on interests and concerns of the public (very controversial).
Pusztai A, Bardocz S, Ewen SWB (2003) Genetically Mofified Foods: Potential Human Health Effects. In: d’Mello JPF,
(ed) Food Safety: Contaminants and Toxins. CAB International
Straub AJ, Hertel C, Hammes P W (1999). The fate of recommbinat DNA in thermally treated fermented sausages. Eur.
Food research.Techno.210: 62-67
33
Intro
Food
Epigenome
Method
Implication
J
G ou G
Tr M rna M
an O- l-p O
di sge inv ap -M
R P rty ni as er
ou ro t c io (1 o
nd m ric M n ( :0 ns
up o-c ks ais 1:0 6:3 a
-to lip (1 (1 8: 8 nt
xi (1 :38 :32 38 –1: o
ci :4 :0 :0 –1 0
ty 0: 0 0 : 8:
(1 57 –1 –1 09 40
:4 – :4 :3 :2 )
5: 1: 0 3: 0)
35 41 :2 55
–1 :36 5) )
:4 )
7:
00
)
Processing (8c/8)
Heritage, 2004
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Madl
34
For example, tinkering with the genes of a tomato may not stop at that tomato, but could alter the
entire biosphere in ways that we cannot foresee. Already there is a study that shows that when
humans digest genetically modified foods, the artificially created genes transfer into and alter
the character of the beneficial bacteria in the intestine [Heritage 2004; Netherwood, et al,
2004]. Similarly, gene transfer among genetically engineered agricultural crops and surrounding
native species has given rise to highly resistant species deemed superweeds (for epigenetic
modifications see Caulerpa taxifolia) [Milius 2003; Haygood, et al, 2003; Desplanque, et al,
2002; Spencer and Snow 2001]
Image: possible route for transfer of DNA from plant cells in the human diet to intestinal bacteria.
Some DNA in food is degraded during cooking and processing, but the remainder is ingested
intact. Consumed DNA is largely hydrolyzed during digestion. Netherwood et al. provide
evidence that intact transgenic DNA can be recovered in the human ileum and taken up by
bacteria in this environment.
Source: Lipton B. (2005). Biology of Belief. Elite Books p.45
Heritage, J. (2004). The fate of transgenes in the human gut. Nature Biotechnology 22, 170-172.
Netherwood T., Martín-OrÚe S.M., O'Donnell A.G., Gockling S., Graham J., Mathers J.C.,
Gilbert H.J. (2004) Assessing the survival of transgenic plant DNA in the human gastrointestinal
tract. Nature Biotechnology 22, 204-209.
34
Intro
Food
Epigenome
Method
Implication
Microbiome (1/12)
The gut-microbiome:
• Eversion of outer environment to a culture
microorganisms under controlled conditions
(e.g. T, rH, pH, pO2, pCO2).
• coordinated microbial activity (homeostasis)
• sustained by gut mucosa
• a downscaled Ecosystem of Endosymbionts
Exchange of energy, matter and information (!)
Norretranders, 1998
21-Aug-15
Madl
35
The person is rooted in the planet. The relationship between the /and the Me is
also the relationship between the conscious person and the planet: How-ever vast
the quantity of information we receive through the outer surface of the body and
its senses, it is as nothing compared to the enormous flow of information
constantly being exchanged across the inner surface: the lungs and the
gastrointestinal system. We breathe and eat and thus exchange enormous
quantities of matter, energy, and information with the earth as a living system ….
Originally, the evolution of life led to the formation of microorganisms such as
bacteria, which developed properties that ensured their survival. At first the
bacteria tried to eat or infect each other. But instead of one bacteria emerging
victorious, they ended up cooperating. Together, two such organisms influenced
each other so much that they developed a symbiotic relationship and could not
survive without each other. Symbiotic relationships are common in nature, but
what made Margulis's idea special was that they could exist within the cells—
i.e., inside the living organisms themselves. An organism could thus consist of an
internal cooperation: an endosymbiosis, with endo mean-ing "inside."
Image: The inner surface. A stream of matter flows through man from lips to the
other end. A very big amount of information is exchanged across this inner
surface to Gaia.
Source: Norretranders T. 1998, The User Illusion. Penguin Books. Harmondsworth, Middlesex, England.
35
Intro
Food
Epigenome
Method
Implication
Microbiome (2/12)
Environmental
influences on gutmicrobiome:
• gut-microbiome is the
interface b/w
environment & body
• mibrobiome releasea
both beneficial a well as
toxic products
• Selective pressure via
diatery preferences,
drugs, and pollutants
Zhao, 2013
21-Aug-15
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36
The gut microbiota has been linked with chronic diseases such as obesity in humans. However,
the demonstration of causality between constituents of the microbiota and specific diseases
remains an important challenge in the field. In this Opinion article, using Koch痴 postulates as a
conceptual framework, I explore the chain of causation from alterations in the gut microbiota,
particularly of the endo- toxin-producing members, to the development of obesity in both rodents
and humans. I then propose a strategy for identifying the causative agents of obesity in the human
microbiota through a combination of microbiome-wide association studies, mechanistic analysis
of host responses and the reproduction of diseases in gnotobiotic animals.
Evans proposed a modified version as a unified concept for establishing causation of a putative
cause (be it biotic or abiotic in nature) in infectious or non-infectious diseases. In this concept,
three kinds of evidence are required to support causation:
(i) an association between the disease phenotypes and the presence of the cells or genetic material
of the putative cause, cross-sectionally and/or longitudinally;
(ii) the reproduction or reduction of the disease phenotypes by experimental addition or removal
of the putative cause in humans or animals;
(iii) and the occurrence of host molecular responses that mechanistically connect the presence of
the putative cause to the occurrence of the disease, for the whole concept to make biological or
epidemiological sense.
Image: Human health is influenced by interactions among the gut microbiota, the host and the
environment. Humans are supraorganisms consisting of both human cells and microbial cells,
particularly the gut microbiota. The gut microbiota interacts with host genetics and the
environment (mainly diet) to influence the health of the human host. On the one hand, the gut
microbiota releases toxins, such as lipopolysaccharides, and beneficial metabolites, such as
vitamins and short-chain fatty acids, to damage or nourish humans, respectively. On the other
hand, human genetics also imposes selective pressures on the gut microbiota through innate
immunity or nutrient availability. The diet and particular drugs have a greater potential to shape
the structure and function of the gut microbiota than host genetics, thus influencing the health
state of the supraorganism.
Source: Zhao L. (2013). The gut microbiota and obesity: from correlation to causality. Nat Rev Microbiol. Vol.11(9):639647.
36
Intro
Food
Epigenome
Method
Implication
Microbiome (3/12)
Ecotone of various bacterial species:
(DNA extracted from fecal samples)
•
•
•
•
•
•
100·E12 microbial cells in the gut
>1·E3 different strains in the gut
responsible for gut homeostasis
99.1% of genes are of bacterial origin,
0.8% of archaeal origin
0.1% of eukaryotic and viral origins
Any misbalance detunes gut-homeostasis &
facilitates proliferation of pathogens
Qin et al., 2010
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37
To understand the impact of gut microbes on human health and well-being it is
crucial to assess their genetic potential. Here we describe the Illumina-based
metagenomic sequencing, assembly and characterization of 3.3 million nonredundant microbial genes, derived from 576.7 gigabases of sequence, from
faecal samples of 124 European individuals. The gene set, approx. 150 times
larger than the human gene complement, contains an overwhelming majority of
the prevalent (more frequent) microbial genes of the cohort and probably includes
a large proportion of the prevalent human intestinal microbial genes. The genes
are largely shared among individuals of the cohort. Over 99% of the genes are
bacterial, indicating that the entire cohort harbours between 1,000 and 1,150
prevalent bacterial species and each individual at least 160 such species, which
are also largely shared. We define and describe the minimal gut metagenome and
the minimal gut bacterial genome in terms of functions present in all individuals
and most bacteria, respectively.
Image: Relative abundance of 57 frequent microbial genomes among individuals
of the cohort. See Fig. 2c for definition of box and whisker plot.
Source: NZZ – die Macht der Bakterien (13. Sept. 2012)
Qin J1, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh C, Nielsen T, Pons N, Levenez F, Yamada T, Mende DR, Li
J, Xu J, Li S, Li D, Cao J, Wang B, Liang H, Zheng H, Xie Y, Tap J, Lepage P, Bertalan M, Batto JM, Hansen T, Le
Paslier D, Linneberg A, Nielsen HB, Pelletier E, Renault P, Sicheritz-Ponten T, Turner K, Zhu H, Yu C, Li S, Jian M,
Zhou Y, Li Y, Zhang X, Li S, Qin N, Yang H, Wang J, Brunak S, Doré J, Guarner F, Kristiansen K, Pedersen O, Parkhill J,
Weissenbach J; MetaHIT Consortium, Bork P, Ehrlich SD, Wang J. (2010). A human gut microbial gene catalogue
established by metagenomic sequencing. Nature, Vol.464(7285):59-65.
37
Intro
Food
Epigenome
Method
Implication
Microbiome (4/12)
Emotions:
fermented milk product with probiotic
properties affected
• microbiome species composition
• blood metabolite levels which in turn
• affects amino-acid & polysaccharide m
etabolism
“
ed
Effects on brain is seen in:
nd
-fu
• various regions that control central
E
N
processing of emotion and
NOsensation
DA
fun
c
n
tio
al
fo
dy
stu
”
od
Tillisch et al., 2013
21-Aug-15
Madl
38
Changes in gut microbiota have been reported to alte signaling mechanisms,
emotional behavior, and visceral nociceptive reflexes in rodents. However,
alteration of the intestinal microbiota with antibiotics or probiotics has not been
shown to produce these changes in humans. We investigated whether
consumption of a fermented milk product with probiotic r (FMPP) for 4 weeks by
healthy women altered brain intrinsic connectivity or responses to emotional
attention tasks.
Several studies have demonstrated that the normal gut flora as well as the
ingestion of probiotics can significantly alter blood metabolite levels, related to
amino acids and to polysaccharide metabolism
Image: Regions showing reduced activity in response to an emotional faces a
ntion task after FMPP intervention are shown, with significant regions d arcated.
Source: Tillisch K, Labus J, Kilpatrick L, Jiang Z, Stains J, Ebrat B, Guyonnet D, Legrain-Raspaud S, Trotin B, Naliboff
B, Mayer EA. (2013) Consumption of fermented milk product with probiotic modulates brain activity. Gastroenterology,
Vol.144(7):1394-401.
38
Intro
Food
Epigenome
Method
Implication
Microbiome (5/12)
Diet:
and the innate immunity
• modified gut microbiota
Legend
LF/PP: low-fat, plant
polysaccharide-rich diet
P: post-natal day
Turnbach er al., 2009
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39
Diet and nutritional status are among themost importantmodifiable determinants of human health.
The nutritional value of food is influenced in part by a person’s gut microbial community
(microbiota) and its component genes (microbiome). Unraveling the interrelations among diet, the
structure and operations of the gut microbiota, and nutrient and energy harvest is confounded by
variations in human environmental exposures, microbial ecology, and genotype. To help
overcome these problems, we created a well-defined, representative animal model of the human
gut ecosystem by transplanting fresh or frozen adult human fecal microbial communities into
germ-free C57BL/6J mice. Culture-independent metagenomic analysis of the temporal, spatial,
and intergenerational patterns of bacterial colonization showed that these humanized mice were
stably and heritably colonized and reproduced much of the bacterial diversity of the
donor’smicrobiota. Switching from a low-fat, plant polysaccharide–rich diet to a high-fat, highsugar “Western” diet shifted the structure of the microbiota within a single day, changed the
representation of metabolic pathways in the microbiome, and altered microbiome gene
expression. Reciprocal transplants involving various combinations of donor and recipient diets
revealed that colonization history influences the initial structure of themicrobial community but
that these effects can be rapidly altered by diet. Humanizedmice fed the Western diet have
increased adiposity; this trait is transmissible via microbiota transplantation. Humanized
gnotobioticmicewill be useful for conducting proof-of-principle “clinical trials” that test the
effects of environmental and genetic factors on the gut microbiota and host physiology.
Image: Postnatal assembly of the humanized gut microbiota. (A) Rarefaction curves
measuring bacterial diversity in the fecal communities. (B) Taxonomic distribution [RDP
level 3 (27)] of the gut microbiota sampled from mice from P14 to P85. Values represent
the average relative abundance across all samples within a given
Source: Turnbaugh PJ, Ridaura VK, Faith JJ, Rey FE, Knight R, Gordon JI. (2009). The effect of diet on the human gut
microbiome: a metagenomic analysis in humanized gnotobiotic mice. Sci Transl Med. Vol.1(6):6ra14.
39
Intro
Food
Epigenome
Method
Implication
Microbiome (6/12)
Health:
and innate immunity
• diet alters the gut microbiota
• the signature of a ‘healthy gut‘ and
changing the microbiota towards a healthy
composition improves human health.
Greiner & Bäckhed., 2011
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40
The human gut is home to a vast number of bacteria, the microbiota, whose
genomes complement our own set of genes. The gut microbiota functions at the
intersection between host genotype and diet to modulate host physiology and
metabolism, and recent data have revealed that the gut microbiota can affect
obesity. The gut microbiota contributes to host metabolism by several
mechanisms including increased energy harvest from the diet, modulation of lipid
metabolism, altered endocrine function, and increased inflammatory tone. The
gut microbiota could thus be considered to be an environmental factor that
modulates obesity and other metabolic diseases.
Image: The gut microbiota suppresses enterocyte expression of Angptl4; this
alleviates LPL inhibition and promotes LPL-mediated triglyceride storage in
adipose tissue. In addition, reduced Angptl4 levels together with diminished
activation of AMPK reduce fatty acid oxidation in skeletal muscle. The gut
microbiota has also direct effects on enteroendocrine L-cells: microbially
generated short-chain fatty acids (SCFAs) bind to the G-protein-coupled receptor
(GPCR) Gpr41 which stimulates secretion of the gut hormone PYY. Secretion of
PYY leads to reduced intestinal transit, increased energy harvest, and stimulates
hepatic lipogenesis. The gut microbiota generates secondary bile acids that are
the major ligands for the GPCR TGR5. Stimulation of TGR5 enhances GLP-1
secretion, and this promotes increased insulin secretion, satiety, and reduced
gastric emptying.
Source: Greiner T, Bäckhed F. (2011) Effects of the gut microbiota on obesity and glucose homeostasis. Trends
Endocrinol Metab. Vol. 22(4):117-123.
40
Intro
Food
Epigenome
Method
Implication
Microbiome (7/12)
Health:
and acquired (gut)immunity
• Biocommunication of bacteria via pilus
• exchange of drug-resistancy via plasmids
(e.g. antibiotic resistance)
Kruse & Sorum., 1994
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41
Image:
Scienceprofonline.com/microbiology/bacterial-genetics-plasmid-dnaconjugation-gene-transfer.html
Source: Kruse H, Sorum H (1994). Transfer of Multiple FDrug Resistance Plasmids between Bacteria of Diverse Origins
in Natural Microenvironments. Applied and Environ. Microbiology Vol.60(11): 4015-4021
41
Intro
Food
Epigenome
Method
Implication
Microbiome (8/12)
Asthma:
and fiber-rich diet induces
• boost in Bacteroidaceae &
Bifidobacteria
• yield short- fatty acids (sFA)
• sFA migrate to bone marrow
• suppress over-expression of
immune cells
Trompete et al., 2014
15-08-21
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42
Metabolites from intestinal microbiota are key determinants of host-microbe
mutualism and, consequently, the health or disease of the intestinal tract.
However, whether such host-microbe crosstalk influences inflammation in
peripheral tissues, such as the lung, is poorly understood. We found that dietary
fermentable fiber content changed the composition of the gut and lung
microbiota, in particular by altering the ratio of Firmicutes to Bacteroidetes. The
gut microbiota metabolized the fiber, consequently increasing the concentration
of circulating short-chain fatty acids (SCFAs). Mice fed a high-fiber diet had
increased circulating levels of SCFAs and were protected against allergic
inflammation in the lung, whereas a low-fiber diet decreased levels of SCFAs and
increased allergic airway disease. Treatment of mice with the SCFA propionate
led to alterations in bone marrow hematopoiesis that were characterized by
enhanced generation of macrophage and dendritic cell (DC) precursors and
subsequent seeding of the lungs by DCs with high phagocytic capacity but an
impaired ability to promote T helper type 2 (TH2) cell effector function. The
effects of propionate on allergic inflammation were dependent on G proteincoupled receptor 41 (GPR41, also called free fatty acid receptor 3 or FFAR3), but
not GPR43 (also called free fatty acid receptor 2 or FFAR2). Our results show
that dietary fermentable fiber and SCFAs can shape the immunological
environment in the lung and influence the severity of allergic inflammation.
Image: not yet accessible as file is not open access
http://www.nature.com/nm/journal/v20/n2/images/nm.3472-F1.jpg
….
Source: Trompette A, Gollwitzer ES, Yadava K, Sichelstiel AK, Sprenger N, Ngom-Bru C, Blanchard C, Junt T, Nicod
TP, Harris NL, Marsland BJ (2014) Gut microbiota metabolism of dietary fiber influences allergic airway disease and
hematopoiesis, Nature Medicine, doi:10.1038/nm.3444
42
Intro
Food
Epigenome
Method
Implication
Microbiome (9/12)
Obesity:
and faecal transplantation in rhodents modify
risk of obeisity
• from lean donors to obese recipients
• from obese donors to lean recipients
.
Ridaura et al., 2013
15-08-21
Madl
43
The role of specific gut microbes in shaping body composition remains unclear. We transplanted
fecal microbiota from adult female twin pairs discordant for obesity into germ-free mice fed lowfat mouse chow, as well as diets representing different levels of saturated fat and fruit and
vegetable consumption typical of the U.S. diet. Increased total body and fat mass, as well as
obesity-associated metabolic phenotypes, were transmissible with uncultured fecal communities
and with their corresponding fecal bacterial culture collections. Cohousing mice harboring an
obese twin‘s microbiota (Ob) with mice containing the lean co-twin‘s microbiota (Ln) prevented
the development of increased body mass and obesity-associated metabolic phenotypes in Ob cage
mates. Rescue correlated with invasion of specific members of Bacteroidetes from the Ln
microbiota into Ob microbiota and was diet-dependent. These findings reveal transmissible, rapid,
and modifiable effects of diet-by-microbiota interactions
Image: Reliable replication of human donor microbiota in gnotobiotic mice. (A) Features of the
four discordant twin pairs. (B) Assembly of bacterial communities in mice that had received intact
and uncultured fecal microbiota transplants from the obese and lean co-twins in DZ pair 1. (C)
Body composition, defined by QMR, was performed 1 day and 15 dpc of each mouse in each
recipient group. Mean values (T SEM) are plotted for the percent increase in fat mass and lean
body mass at 15 dpc for all recipient mice of each of the four obese co-twins‘ or lean co-twins‘
fecal microbiota, normalized to the initial body mass of each recipient mouse. Driven by a
significant difference in adiposity and total body mass between mice colonized with a lean or
obese co-twin donor‘s fecal microbiota. (D) Mean values (T SEM) are plotted for the percent
change in fat mass at 15 dpc for all recipient mice of each of the four obese co-twins‘ or lean cotwins‘ fecal microbiota. (E) More prolonged time course study for recipients of fecal microbiota
from co-twins in discordant DZ pair 1.
Source: Ridaura VK, Faith JJ, Rey FE, Cheng J, Duncan AE, Kau AL, Griffin NW, Lombard V, Henrissat B, Bain JR,
Muehlbauer MJ, Ilkayeva O, Semenkovich CF, Funai K, Hayashi DK, Lyle BJ, Martini MC, Ursell LK, Clemente JC, Van
Treuren W, Walters WA, Knight R, Newgard CB, Heath AC, Gordon JI. (2013) Gut microbiota from twins discordant for
obesity modulate metabolism in mice. Science. Vol.341(6150): 1079-1089.
43
Intro
Food
Epigenome
Method
Implication
Microbiome (10a/12)
Obeisity:
and a missing protein (Toll-like receptor-5) –
a component of the innate immune system –
it induces:
•
•
•
•
highly irritated intestine
obesity
high blood pressure
diabetes – type 2
Vijar-Kumar et al., 2010
15-08-21
Madl
44
Metabolic syndrome is a group of obesity-related metabolic abnormalities that
increase an individual’s risk of developing type 2 diabetes and cardiovascular
disease. Here, we show that mice genetically deficient in Toll-like receptor 5
(TLR5), a component of the innate immune system that is expressed in the gut
mucosa and that helps defend against infection, exhibit hyperphagia and develop
hallmark features of metabolic syndrome, including hyperlipidemia,
hypertension, insulin resistance, and increased adiposity. These metabolic
changes correlated with changes in the composition of the gut microbiota, and
transfer of the gut microbiota from TLR5-deficient mice to wild-type germ-free
mice conferred many features of metabolic syndrome to the recipients. Food
restriction prevented obesity, but not insulin resistance, in the TLR5-deficient
mice. These results support the emerging view that the gut microbiota contributes
to metabolic disease and suggest that malfunction of the innate immune system
may promote the development of metabolic syndrome
Image: T5KO mice develop obesity. T5KO mice and WT littermates were
monitored for 20 weeks. Abdominal photograph of representative 20-week-old
male mice.
Source: Vijay-Kumar M, Aitken JD, Carvalho FA, Cullender TC, Mwangi S, Srinivasan S, Sitaraman SV, Knight R, Ley
RE, Gewirtz AT. (2010). Metabolic syndrome and altered gut microbiota in mice lacking Toll-like receptor 5. Science.
Vol.328(5975):228-31.
44
Intro
Food
Epigenome
Method
Implication
Microbiome (10b/12)
Obeisity
Epigenetic Imprinting (paramutation):
Mothers treated w/ gastro-intestinal bypass (to
loose weight)
• Investigated 50 kids from 20 obese mothers
• kids of obese mothers tend to be likewise
obese
• some received gastro-intestinal bypass
(GIB)
• these kids developed normally
• approx. 5700 genes differently methylated
among siblings (before & after mother
underwent GIB)
Ng et al., 2010
15-08-21
Madl
45
Obesity and overnutrition during pregnancy affect fetal programming of adult disease. Children born after maternal
bariatric gastrointestinal bypass surgery (AMS) are less obese and exhibit improved cardiometabolic risk profiles carried
into adulthood compared with siblings born before maternal surgery (BMS). This study was designed to analyze the impact
of maternal weight loss surgery on methylation levels of genes involved in cardiometabolic pathways in BMS and AMS
offspring. Differential methylation analysis between a sibling cohort of 25 BMS and 25 AMS (2–25 y-old) offspring from
20 mothers was conducted to identify biological functions and pathways potentially involved in the improved
cardiometabolic profile found in AMS compared with BMS offspring. A total of 5,698 genes were differentially
methylated between BMS and AMS siblings, exhibiting a preponderance of glucoregulatory, inflammatory, and vascular
disease genes.
The global prevalence of obesity is increasing across most ages in both sexes. This is contributing to the early emergence
of type 2 diabetes and its related epidemic1, 2. Having either parent obese is an independent risk factor for childhood
obesity3. Although the detrimental impacts of diet-induced maternal obesity on adiposity and metabolism in offspring are
well established4, the extent of any contribution of obese fathers is unclear, particularly the role of non-genetic factors in
the causal pathway. Here we show that paternal high-fat-diet (HFD) exposure programs β-cell ‘dysfunction’ in rat F female
offspring. Chronic HFD consumption in Sprague–Dawley fathers induced increased body weight, adiposity, impaired
glucose tolerance and insulin sensitivity. Relative to controls, their female offspring had an early onset of impaired insulin
secretion and glucose tolerance that worsened with time, and normal adiposity. Paternal HFD altered the expression of 642
pancreatic islet genes in adult female offspring; genes belonged to 13 functional clusters, including cation and ATP
binding, cytoskeleton and intracellular transport. Broader pathway analysis of 2,492 genes differentially expressed
demonstrated involvement of calcium-, MAPK- and Wnt-signalling pathways, apoptosis and the cell cycle.
Hypomethylation of the Il13ra2 gene, which showed the highest fold difference in expression (1.76-fold increase), was
demonstrated. This is the first report in mammals of non-genetic, intergenerational transmission of metabolic sequelae of a
HFD from father to offspring.
Image: a, Body weight (control, HFD: n = 8 and 9, respectively). b, Specific growth rate (SGR, change in body
weight/body weight; n = 8 and 9, respectively). c, Cumulative energy intake (n = 9 and 7, respectively). d–g Blood glucose
(d) and plasma insulin (e) during a glucose tolerance test at 6 weeks (n = 8 and 8, respectively) and 12 weeks (f, g) (n = 5
and 7, respectively). h, Insulin resistance index (glucose (mM) × insulin (ng ml−1) × 0.0417/22.5) at 12 weeks. i, Blood
glucose during an insulin tolerance test (0.5 U kg−1) at 11 weeks (n = 8 and
9, respectively).
Source: Guénard F, Deshaiesb Y, Cianfloneb K, Krald JG, Marceauc P, Vohla MC (2012) Differential methylation in
glucoregulatory genes of offspring born before vs. after maternal gastrointestinal bypass surgery. PNAS, vol.110(28)
11439 -11444.
Ng SF, Ruby C, Lin Y, Laybutt DR, Barres R, Owens JA, Morris MJ (2010) Chronic high-fat diet in fathers
programs β-cell dysfunction in female rat offspring. Nature Vol. 467: 963 -966
45
Intro
Food
Epigenome
Method
Implication
Microbiome (11/12)
Obesity:
Epigenetic activation
SNPs (single nucleotide polymorphisms)
morphologically affect:
• FTO-gene (an intron not coding a
protein)
• that controls IRX3-gene (active during
embryo stage)
• deactivated, it reduced the body’s ability
to store fat (IRX3 KO)
Ctrl: control (wild type)
KO …. knock out variant
Smeno et al., 2014
15-08-21
Madl
46
Genome-wide association studies (GWAS) have reproducibly associated variants within
introns of FTO with increased risk for obesity and type 2 diabetes (T2D)1–3. Although
the molecular mechanisms linking these noncoding variants with obesity are not
immediately obvious, subsequent studies in mice demonstrated that FTO expression
levels influence bodymass and composition phenotypes4–6.However, no direct
connection between the obesity-associated variants and FTO expression or function has
been made7–9. Here we show that the obesity-associated noncoding sequences within
FTO are functionally connected, at megabase distances, with the homeobox gene IRX3.
The obesity-associated FTO region directly interacts with the promoters of IRX3 as well
as FTO in the human, mouse and zebrafish genomes. Furthermore, long-range enhancers
within this region recapitulate aspects of IRX3 expression, suggesting that the obesityassociated interval belongs to the regulatory landscape of IRX3.Consistentwith this,
obesity-associated single nucleotide polymorphisms are associated with expression
ofIRX3, but not FTO, in human brains. A direct link between IRX3 expression and
regulation of body mass and composition is demonstrated by a reduction in body weight
of 25 to 30% in Irx3-deficientmice, primarily through the loss of fatmass and increase inb
asal metabolic rate with browning of white adipose tissue. Finally, hypothalamic
expression of a dominant negative form of Irx3 reproduces the metabolic phenotypes of
Irx3-deficientmice. Our data suggest thatIRX3 is a functional long-range target of
obesity-associated variants within FTO and represents a novel determinant of body mass
and composition.
Image: Figure 3 | Irx3-deficient mice are leaner and are protected against dietinduced
obesity. Sections of inguinal white adipose tissue (IWAT; subcutaneous), perigonadal
WAT (PWAT; visceral), brown adipose tissue (BAT), and liver from High Fat Diet mice.
Source: Smemo S, Tena JJ, Kim KH, Gamazon ER, Sakabe NJ, Gómez-Marín C, Aneas I, Credidio FL, Sobreira DR,
Wasserman NF, Lee JH, Puviindran V, Tam D, Shen M, Son JE, Vakili NA, Sung HK, Naranjo S, Acemel RD,
Manzanares M, Nagy A, Cox NJ, Hui CC, Gomez-Skarmeta JL, Nóbrega MA. (2014) Obesity-associated variants within
FTO form long-range functional connections with IRX3. Nature 507(7492): 371–375
46
Intro
Food
Epigenome
Method
Implication
Microbiome (12a/12)
Maternal transfer:
From mother to infant to boost infant
colonization
• Limited transmigration of maternal
microbes through placenta & amniotic
fluid;
• Substantial exposure during vaginal
delivery;
• Breastfeed as direct source of bacteria
via skin & milk;
Rautava et al., 2012
15-08-21
Madl
47
Interaction with colonizing intestinal bacteria is essential for healthy intestinal
and immunological development in infancy. Advances in understanding early
host–microbe interactions indicate that this early microbial programming begins
in utero and is substantially modulated by mode of birth, perinatal antibiotics and
breastfeeding. Furthermore, it has become evident that this stepwise microbial
colonization process, as well as immune and metabolic programming by the
microbiota, might have a long-lasting influence on the risk of not only
gastrointestinal disease, but also allergic, autoimmune and metabolic disease, in
later life. Modulating early host–microbe interaction by maternal probiotic
intervention during pregnancy and breastfeeding offers a promising novel tool to
reduce the risk of disease. In this Review, we describe the current body of
knowledge regarding perinatal microbial contact, initial intestinal colonization
and its association with human disease, as well as means of modulating early
host–microbe interaction to reduce the risk of disease in the child.
The fetus comes into contact with microbes originating in the maternal gut
through the placenta and amniotic fluid. A massive inoculum of maternal bacteria
is encountered during vaginal delivery, which is also associated with increased
maternal intestinal permeability and translocation of gut bacteria into breast milk.
Breastfeeding not only modulates neonatal bacterial colonization and immune
maturation, but is a direct source of maternal bacteria. After birth, skin-to-skin
contact and nursing ensures direct transfer of maternal bacteria to the infant to
enhance healthy immune and metabolic maturation.
Image: The gut microbiota programmes host health—from mother to infant.
Source: Rautava S, Luoto R, Salminen S, Isolauri E (2012). Microbial contact during pregnancy, intestinal colonization
and human disease. Nature Reviews Gastroenterology and Hepatology Vol.9, 565-576
47
Intro
Food
Epigenome
Method
Implication
Microbiome (12b/12)
Maternal transfer:
From mother to infant
• Intrauterine
• Caesarean / vaginal
• Breast or formula
feeding
• Medical treatment
• Familial contamination
Matamoros et al., 2013
15-08-21
Madl
48
Throughout the human lifetime, the intestinal microbiota performs vital
functions, such as barrier function, metabolic reactions, trophic effects, and
maturation of the host's innate and adaptive immune responses. Development of
the intestinal microbiota in infants is characterized by rapid and large changes in
microbial abundance, diversity, and composition. These changes are influenced
by medical, cultural, and environmental factors such as mode of delivery, diet,
familial environment, diseases, and therapies used. Thus, it is nearly impossible
to define a universal standard for intestinal colonization and development of the
intestinal microbiota. This review discusses recent data on the early colonization
of the gut by microbial species, development of the intestinal microbiota, and its
impact on health.
Image: Impact of external factors on the intestinal microbiota of the infant. Green
arrows show beneficial modification; red arrows show modification considered
negative for healthy development.
Source: Matamoros S, Gras-Leguen C, Le Vacon F, Potel G, de LaCochetiere MF. (2013) Development of intestinal
microbiota in infants and its impact on health. Trends Microbiol. Vol.21(4): 167-173.
48
Intro
Food
Epigenome
Method
Implication
Microbiome (12c/12)
Maternal transfer:
modulating the infants
mibrobiome & future health
• communities in natural
borns resemble vaginal
microbiota (Lactobacillus,
Prevotella, or Sneathia
spp. etc,),
• communities among Csection babies resemble
maternal skin surface
(Staphylo-coccus, Corynebacterium, Propionibact.
spp. etc.)
15-08-21
Dominguez-Bello et al., 2010
Madl
bacterial community
characterization via
16S rRNA gene
pyrosequencing
49
Upon delivery, the neonate is exposed for the first time to a wide array of microbes from a variety
of sources, including maternal bacteria. Although prior studies have suggested that delivery mode
shapes the microbiota's establishment and, subsequently, its role in child health, most researchers
have focused on specific bacterial taxa or on a single body habitat, the gut. Thus, the initiation
stage of human microbiome development remains obscure. The goal of the present study was to
obtain a community-wide perspective on the influence of delivery mode and body habitat on the
neonate's first microbiota. We used multiplexed 16S rRNA gene pyrosequencing to characterize
bacterial communities from mothers and their newborn babies, four born vaginally and six born
via Cesarean section. Mothers’ skin, oral mucosa, and vagina were sampled 1 h before delivery,
and neonates’ skin, oral mucosa, and nasopharyngeal aspirate were sampled <5 min, and
meconium <24 h, after delivery. We found that in direct contrast to the highly differentiated
communities of their mothers, neonates harbored bacterial communities that were undifferentiated
across multiple body habitats, regardless of delivery mode. Our results also show that vaginally
delivered infants acquired bacterial communities resembling their own mother's vaginal
microbiota, dominated by Lactobacillus, Prevotella, or Sneathia spp., and C-section infants
harbored bacterial communities similar to those found on the skin surface, dominated by
Staphylococcus, Corynebacterium, and Propionibacterium spp. These findings establish an
important baseline for studies tracking the human microbiome's successional development in
different body habitats following different delivery modes, and their associated effects on infant
health.
Image: Bacterial 16S rRNA gene surveys reveal that the first microbiotas of human newborns are
primarily structured by delivery mode. (A) Communities clustered using principal coordinates
analysis of the unweighted UniFrac distance matrix. PC1 and PC2 are plotted on x- and y-axes.
Each point corresponds to a community colored according to the mother's body habitat or the
newborn's delivery mode. All newborn body habitats are shown. The percentage of variation
explained by the plotted principal coordinates is indicated on the axes. The white arrow indicates
a pair of superimposed points. Vaginal samples were not obtained from two of the mothers who
delivered by C-section. (B) Average relative abundances of the dominant taxa found in this study
in aggregated samples. (C) Relative abundances of the 20 most abundant taxa in mothers’ vaginal
communities and in the babies they delivered vaginally. Sequences were classified to highest
taxonomic level to which they could be confidently assigned.
Source: Dominguez-Bello MG, Costello EK, Contreras M, Magris M, Hidalgo G, Fierer N,
Knight R. (2010) Delivery mode shapes the acquisition and structure of the initial microbiota
across multiple body habitats in newborns. PNAS Vol.107(26):11971-11975.
49
Intro
cro
Mi
Food
Epigenome
Method
Implication
Microbiome (12d/12)
VD
-D
h
t
bir
Maternal transfer:
the mother’s vaginal bacterial
community is more similar to
her own baby’s microbiota
than to the microbiota of other
vaginally delivered babies.
Skin bacterial communities of
Caesarean-section mothers
were no equal to their own
babies than to the other Cbabies.
Dominguez-Bello et al., 2010
15-08-21
Madl
50
Upon delivery, the neonate is exposed for the first time to a wide array of microbes from
a variety of sources, including maternal bacteria. Although prior studies have suggested
that delivery mode shapes the microbiota's establishment and, subsequently, its role in
child health, most researchers have focused on specific bacterial taxa or on a single body
habitat, the gut. Thus, the initiation stage of human microbiome development remains
obscure. The goal of the present study was to obtain a community-wide perspective on
the influence of delivery mode and body habitat on the neonate's first microbiota. We
used multiplexed 16S rRNA gene pyrosequencing to characterize bacterial communities
from mothers and their newborn babies, four born vaginally and six born via Cesarean
section. Mothers’ skin, oral mucosa, and vagina were sampled 1 h before delivery, and
neonates’ skin, oral mucosa, and nasopharyngeal aspirate were sampled <5 min, and
meconium <24 h, after delivery. We found that in direct contrast to the highly
differentiated communities of their mothers, neonates harbored bacterial communities
that were undifferentiated across multiple body habitats, regardless of delivery mode. Our
results also show that vaginally delivered infants acquired bacterial communities
resembling their own mother's vaginal microbiota, dominated by Lactobacillus,
Prevotella, or Sneathia spp., and C-section infants harbored bacterial communities
similar to those found on the skin surface, dominated by Staphylococcus,
Corynebacterium, and Propionibacterium spp. These findings establish an important
baseline for studies tracking the human microbiome's successional development in
different body habitats following different delivery modes, and their associated effects on
infant health.
Image: The effect of delivery mode on the direct transmission of bacteria from mother to
newborn. Average (±SEM) weighted UniFrac distance for pairwise comparisons between
(A) vaginal microbiota of mothers who delivered vaginally, or (B) the skin microbiota of
mothers who delivered via C-section and the microbiotas of the newborn babies. The
maternal microbiota (vagina or skin) was compared with the microbiota of her own baby,
or babies of the same or different delivery mode. Baby samples were from the skin (arms
and forehead), oral mucosa, nasopharyngeal aspirate, and meconium. The mothers’ skin
samples were from both arms.
Source: Dominguez-Bello MG, Costello EK, Contreras M, Magris M, Hidalgo G, Fierer
N, Knight R. (2010) Delivery mode shapes the acquisition and structure of the initial
microbiota across multiple body habitats in newborns. PNAS Vol.107(26):11971-11975.
50
Intro
Food
Epigenome
Method
Implication
Microbiome (12e/12)
Maternal transfer:
Maternal
• lifestyle (smoking, drinking)
• exposure to food, water & air
• obeisity
• hygiene (lack / excessive)
• stress (psychodynamics)
• medication & drug abuse
Matamoros et al., 2013
15-08-21
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51
More than 300 years after Antonie van Leeuwenhoek gave the first description of
microbes that colonize human body surfaces, the re-discovery of this multifaceted
microbial world within our bodies has challenged our principal view on microbes.
Novel sequencing techniques provide a plethora of (meta)genomic data, which
elucidate the unique properties of mircobiota in different subjects. Moreover, the
variety of metabolic and immunologic interactions between the mircobiota and
the host's epithelial surfaces has challenged the paradigm of a unidirectional
interplay between a given pathogen and the host's immune defense. The newly
discovered mechanisms that underlie the symbiosis between the host, specific
colonizers, and the mircobiota as a whole indicate that this colonization is more
than a friendly coexistence. In fact, it represents a complex ecosystem with
implications for the human metabolic homeostasis and immune tolerance. The
resilience of the mircobiota and the capability to maintain a well-established
equilibrium between symbionts and potential pathogens seem to be determining
factors in shaping health or disease.
Maternal lifestyle factors such as dietary habits/obesity, smoking, a poor
microbial environment (e.g. urban lifestyle), and chronic stress during pregnancy
might lower the diversity of maternal mircobiota and decelerate the fetal immune
development. Mode of delivery and immune maturation at birth might have an
impact on the diversity and properties of the neo-/postnatal bacterial colonization.
Neo-/postnatal nutrition, early chronic stressful events, and low microbial
diversity of the living environment (e.g. exaggerated hygiene, frequent and early
use of antibiotics) might hamper the development of a diverse and adaptive
mircobiota, which favors a non-enriched mircobiota accompanied by proinflammatory conditions at the mucosal interfaces, a metabolic imbalance, and
the loss of immune tolerance. This might result in a higher risk for chronic
inflammatory and metabolic diseases in later life.
Image: Pre- and postnatal environmental factors pave the way for later chronic
inflammatory disease through the microbiome.
Source: Pfefferle PI, Renz H. (2014). The mucosal microbiome in shaping health and disease. F1000Prime Rep. Vol.6: 1120
51
Intro
Food
Epigenome
Method
Implication
Aluminium (1/10)
21st century - the Aluminium Age:
• was biologically non-available to the
biochemical evolution until 20th century
• Al enters geochemical cycling - is
deliberately introduced into biopshere
• Al is not required for cellular metabolism
• Al is toxic to life
Exley, 2013
21-Aug-15
Madl
52
Human activities have circumvented the efficient geochemical cycling of
aluminium within the lithosphere and therewith opened a door, which was
previously only ajar, onto the biotic cycle to instigate and promote the
accumulation of aluminium in biota and especially humans. Neither these
relatively recent activities nor the entry of aluminium into the living cycle are
showing any signs of abating and it is thus now imperative that we understand as
fully as possible how humans are exposed to aluminium and the future
consequences of a burgeoning exposure and body burden. The aluminium age is
upon us and there is now an urgent need to understand how to live safely and
effectively with aluminium.
Image: Aluminium's exposome. A schematic which explores relationships
between exposure, immediate targets mediating exposure, sinks and sources of
biologically available aluminium with putative mechanisms of action and finally
excretion of aluminium.
Source: Exley C. (2013). Human exposure to aluminium. Environ. Sci. Processes Impacts, Vol.15:1807-1816.
52
Intro
Food
Epigenome
Method
Implication
Aluminium (2/10)
Al-compounds as food supplements:
Walton, 2012
• 300 BCE, romans coloured wine with it (!)
• Nowadays Al-sulfates used to teat water (> levels of monomeric Al3+)
• Basic variants form precipitates; deprotonated (<pH 5 : Al3+) soluble and most toxic;
pH of selected fluids
• Stomach acid: pH 1
• Lemon juice: pH 2
• Vinegar: pH 3
15-08-21
Madl
53
Aluminum (Al) is a recognized neurotoxin causally linked to several neurodegenerative
diseases with a dementia component. Al has long had a GRAS (Generally Recognized As
Safe) rating by the US FDA, that allows Al salts to be used in food manufacture and
clarification of urban drinking water supplies. Routine ingestion of Al salts throughout
life causes bioavailable Al to accumulate in the brain where it specifically deposits in
regions most vulnerable in Alzheimer’s disease (AD). The main source of Al exposure
for humans is their total dietary Al intake from foods, water, other beverages, and Al
additives. Animal studies provide a parallel in that their feed and water intakes can be
rigorously controlled throughout the life span. Such a study revealed that a significant
proportion of rats, particularly those that consumed Al in an equivalent amount to the
high end of the human total dietary Al range, progressively accumulated Al in their brain,
accompanied by AD-related neuropathology and cognitive deterioration in old age.
•Aluminium chlorohydrate-salt: AlnCl(3n-m)(OH)m is used in deodorants and
antiperspirants and as a coagulant in water purification.
•Aluminium hydroxide, Al(OH)3,
•Hydroxoaluminate: Al(OH)4− anion is known in high pH solutions of Al(OH)3
Inlet: The concentrations of soluble, mononuclear Al ion species, present in aqueous
solutions, change as the pH is raised or lowered. Ionic or free Al3+ is an inorganic
monomer and is regarded as the most bioavailable and toxic Al-species.
Image:Use of Al-salts in processed foods and drinking water; Other uses: to strengthen
dough; swell pastas; bleach flour and cheeses. Al is also included as an ingredient in
reconstituted vegetable protein, as a stabilizer, thickener, acidifying agent, buffer,
neutralizer and texturizer [15]. Calcium supplements, especially those based on oyster
shells, provide about 12 mgAl/day .
Source: Walton JR (2012). Evidence that Ingested Aluminum Additives Contained in Processed Foods and Alum-Treated
Drinking Water are a Major Risk Factor for Alzheimer’s Disease. Current Inorganic Chemistry, Vol. 2: 000-000
53
Intro
Food
Epigenome
Method
Implication
Aluminium (2/10)
Al-compounds as food supplements:
Walton, 2012
• 300 BCE, romans coloured wine with it (!)
• Nowadays Al-sulfates used to teat water (> levels of monomeric Al3+)
• Basic variants form precipitates; deprotonated (<pH 5 : Al3+) soluble and most toxic;
15-08-21
Madl
54
Aluminum (Al) is a recognized neurotoxin causally linked to several neurodegenerative
diseases with a dementia component. Al has long had a GRAS (Generally Recognized As
Safe) rating by the US FDA, that allows Al salts to be used in food manufacture and
clarification of urban drinking water supplies. Routine ingestion of Al salts throughout
life causes bioavailable Al to accumulate in the brain where it specifically deposits in
regions most vulnerable in Alzheimer’s disease (AD). The main source of Al exposure
for humans is their total dietary Al intake from foods, water, other beverages, and Al
additives. Animal studies provide a parallel in that their feed and water intakes can be
rigorously controlled throughout the life span. Such a study revealed that a significant
proportion of rats, particularly those that consumed Al in an equivalent amount to the
high end of the human total dietary Al range, progressively accumulated Al in their brain,
accompanied by AD-related neuropathology and cognitive deterioration in old age.
•Aluminium chlorohydrate-salt: AlnCl(3n-m)(OH)m is used in deodorants and
antiperspirants and as a coagulant in water purification.
•Aluminium hydroxide, Al(OH)3,
•Hydroxoaluminate: Al(OH)4− anion is known in high pH solutions of Al(OH)3
Inlet: The concentrations of soluble, mononuclear Al ion species, present in aqueous
solutions, change as the pH is raised or lowered. Ionic or free Al3+ is an inorganic
monomer and is regarded as the most bioavailable and toxic Al-species.
Image:Use of Al-salts in processed foods and drinking water; Other uses: to strengthen
dough; swell pastas; bleach flour and cheeses. Al is also included as an ingredient in
reconstituted vegetable protein, as a stabilizer, thickener, acidifying agent, buffer,
neutralizer and texturizer [15]. Calcium supplements, especially those based on oyster
shells, provide about 12 mgAl/day .
Source: Walton JR (2012). Evidence that Ingested Aluminum Additives Contained in Processed Foods and Alum-Treated
Drinking Water are a Major Risk Factor for Alzheimer’s Disease. Current Inorganic Chemistry, Vol. 2: 000-000
54
Intro
Food
Epigenome
Method
Implication
Aluminium (3/10)
Epigenetics of
Al-exposure :
• Heterochromatin:
genetically inactive
• Al inhibits eukaryotic gene
transcription
• Al acts as transcriptional
repressor (of A+T-rich
templates)
• Found across species
AT, Arabidopsis thaliana (cress);
LU, Linum usitatissimum (flax);
CE, Caenorhabditis elegans (nematode);
MS, Mus musculus (mouse);
HS, Homo sapiens (human); (L) liver;
(B) brain.
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Lukiw, 2010
55
Averaging 8.1% (w/w) of the earth's crust, aluminum is the most highly abundant
metal in our biosphere, yet has long been thought to serve no essential biological
function. In aqueous solutions, aluminum salts and hydroxides are exceptionally
potent aggregators of biological molecules, often coalescing molecular species to
the point that they precipitate out of solution. A biological function for aluminum
is proposed in which this abundant, high charge density metal cation has a
significant role in biomolecular compaction. Sometimes, molecules ectopically
aggregated by aluminum are associated with pathological conditions. The data
further suggests that a specific consequence of ‚aluminum biocompaction‘ may
be particularly important in the condensation of A + T-rich chromatin domains,
and in silencing the expression of specific kinds of genetic information.
Image: Aluminum content and genetic activity are inversely correlated.
Correlation of interphase heterochromatin status and aluminum content of
chromatin in select eukaryotic nuclei. Eukaryotic nuclei contain complex
arrangements of heterochromatic and euchromatic domains: ‘inactive,
constitutive‘ heterochromatin is associated with the absence of gene expression.
Mean constitutive heterochromatin was assayed for A+T-rich heterochromatic
regions, and heterochromatin was expressed as a percent of total nuclear area;
aluminum content, expressed as μg/g total chromatin.
Source: Lukiw WJ (2010). Evidence supporting a biological role for aluminum in chromatin compaction and epigenetics.
Journal of Inorganic Biochemistry Vol.104: 1010-1012.
55
Intro
Food
Epigenome
Method
Implication
Aluminium (4a/10)
Average personal Al-exposure :
pregnant women suffer often from
gastroesophageal reflux:
• Al-hydroxide is also often used as
antiacids (heartburn, gastro-esophageal
reflux disease)
• Al-hydroxide is a known neurotoxin &
contraindicated in pregnancy
Wikipedia 2014
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56
Antacids either directly neutralize acidity, increasing the pH, or reversibly reduce
or block the secretion of acid by gastric cells to reduce acidity in the stomach.
When gastric hydrochloric acid reaches the nerves in the gastrointestinal mucosa,
they signal pain to the central nervous system. This happens when these nerves
are exposed. In addition to the reduction of gastric acidity, antacids also alter the
profile of prostaglandins produced by gastroduodenal mucosa and this may
promote mucosal healing and be related to its therapeutic effect
Antacids are taken by mouth to relieve heartburn, the major symptom of
gastroesophageal reflux disease, or acid indigestion. Treatment with antacids
alone is symptomatic and only justified for minor symptoms. The treatment of
ulcers resulting from excessive acidity may require H2-receptor antagonists or
proton pump inhibitors, and eradication of H. pylori.
Aluminum hydroxide: may lead to the formation of insoluble aluminiumphosphate-complexes, with a risk for hypophosphatemia and osteomalacia.
Although aluminium has a low gastrointestinal absorption, accumulation may
occur mainly in the presence of renal insufficiency. Aluminium-containing drugs
often cause constipation and are neurotoxic. Aluminium-containing drugs are
contraindicated in pregnancy.
Image: Wyeth amphojel tablets of aluminum hydroxide.
Source: http://en.wikipedia.org/wiki/Antacid
56
Intro
Food
Epigenome
Method
Implication
Aluminium (4b/10)
• Inhalation: 1.4 µg/day
• Ingestion: 1-20 mg/day
• Epidermal: 2 g/day
Franz-cell exposure system to test
transmigration of Aluminium
chlorohydrate (ACH) via dermal layer
Pineau et al., 2012
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Aluminum salts such as aluminum chlorohydrate (ACH) are known for use as an
active antiperspirant agent that blocks the secretion of sweat. A local case report
of hyperaluminemia in a woman using an aluminum-containing antiperspirant for
4 years raises the problem of transdermal absorption of aluminum (Al). Only a
very limited number of studies have shown that the skin is an effective barrier to
transdermal uptake of Al. In accordance with our analytical procedure, the aim of
this study with an in vitro Franz™ diffusion cell was to measure aluminum
uptake from three cosmetic formulations of antiperspirant: the base for an
"aerosol" (38.5% of ACH), a "roll-on" emulsion (14.5% ACH), and a "stick"
(21.2%), by samples of intact and stripped human skin (5 donors). The Al assays
were
performed
by
Zeeman
Electrothermal
Atomic
Absorption
Spectrophotometry (ZEAAS). Following contacts lasting 6, 12 and 24h, the Al
assays showed only insignificant transdermal absorption of Al (≤0.07% of the
quantity of Al deposited) and particularly low cutaneous quantities that varied
according to the formulations (1.8 μg/cm² for "aerosol base" and "stick" - 0.5
μg/cm² for the "roll-on"). On stripped skin, for which only the "stick" formulation
was tested, the measured uptake was significantly higher (11.50 μg/cm² versus
1.81 μg/cm² for normal skin). These results offer reassurance as regards to the use
of antiperspirants for topical application of ACH-containing cosmetic
formulations on healthy skin over a limited time span (24h). On the other hand,
high transdermal Al uptake on stripped skin should compel antiperspirant
manufacturers to proceed with the utmost caution.
Image: Franz™ diffusion cell (static type) to test transmigration of
chlorohydrate-salt: AlnCl(3n-m)(OH)m across skin.
Aluminium
Source: Pineau A, Guillard O, Favreau F, Marrauld A, Fauconneau B. (2012) In vitro study of percutaneous absorption of
aluminum from antiperspirants through human skin in the Franz™ diffusion cell. J. o. Inorg. Biochem., Vol.110: 21-26.
57
Intro
Food
Epigenome
Method
Implication
Aluminium (4c/10)
• Inhalation: 1.4 µg/day
• Ingestion: 1-20 mg/day
• Epidermal: 2 g/day
Exley, 2013
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58
While the evidence to-date is that only a very small proportion of aluminium in
topically-applied antiperspirant enters the bloodstream to ultimately be excreted
via the kidney this observation does not preclude the persistence of such
aluminium within the structures of the skin and neither does it preclude the entry
of this aluminium into the lymphatic system. The nature of the aluminium
compounds which are present in topical applications, the amount of aluminium
which is often applied and the regularity of many such applications must mean
that skin is a significant sink for aluminium and a persistent source of
biologically available aluminium both locally and systemically.
Image: The skin is a sink for topically applied aluminium and will act as a source
of biologically reactive aluminium both to structures within the skin and to the
systemic circulation.
Source: Exley C. (2013). Human exposure to aluminium. Environ. Sci. Processes Impacts, Vol.15:1807-1816.
58
Intro
Food
Epigenome
Method
Implication
Aluminium (5/10)
Hormone Mimicry
induced by Xenobiotics
via:
• high concentrations of a
chemical w/ low binding
affinity to oestrogen
receptors (OR)
• Cocktail of several
compounds w/ low
affinity to OR - acting
synergistically!
Dabre & Fernandez, 2013
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59
Although diet, alcohol, radiation and inherited loss of BRCA1/2 genes have all
been associated with increased incidence, the main identified risk factors are life
exposure to hormones including physiological variations associated with
puberty/pregnancy/menopause, personal choice of use of hormonal
contraceptives and/or hormone replacement therapy. On this basis, exposure of
the human breast to the many environmental pollutant chemicals capable of
mimicking or interfering with oestrogen action should also be of concern.
Hundreds of such environmental chemicals have now been measured in human
breast tissue from a range of dietary and domestic exposure sources including
persistent organo-chlorine pollutants (POPs), polybromi- nated diphenylethers
and polybromobiphenyls, polychlorinated biphenyls, dioxins, alkyl phenols,
bisphenol-A and chlorinated derivatives, as well as other less lipophilic
compounds such as parabens (alkyl esters of p-hydroxybenzoic acid), but studies
investigating any association between raised levels of such compounds and the
development of breast cancer remain inconclusive.
Image: The many ways in which different environmental chemicals may induce
an oestrogenic stimulus to the human breast through a receptor-mediated
mechanism. Colour gradient from black to grey to white indicates a decreasing
contribution to oestrogenic load. Compounds with higher relative binding affinity
(RBA) for the oestrogen receptor only need to be present at lower concentrations.
Source: Darbre PD, Fernandez MF (2013). Environmental oestrogens and breast cancer: long-term low-dose effects of
mixtures of various chemical combinations. J Epidemiol Community Health March Vol.67(3): 203-205.
59
Intro
Food
Epigenome
Method
Implication
Aluminium (6/10)
Hormone Mimicry
induced by Xenobiotics
via:
• high concentrations of a
chemical w/ low binding
affinity to oestrogen
receptors (OR)
• Cocktail of several
compounds w/ low
affinity to OR - acting
synergistically!
Dabre, 2011
15-08-21
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60
Although epidemiological studies conclude that the majority of breast cancers are
environmental in origin, the main underlying environmental causes remain to be
identified. Loss of function of the deoxyribonucleic acid (DNA) repair tumor suppressor
genes breast cancer susceptibility gene 1/2 (BRCA1/2), exposure to excess prolactin,
smoking, diet, alcohol, and radiation have all been identified as risk factors, but lifetime
exposure to estrogen remains the main influence in the development of breast cancer.
Epidemiological studies have linked estrogen exposure to breast cancer incidence through
studies of the effects of age of me- narche/menopause, nulliparity, age of first pregnancy,
practices of breastfeeding, and use of the oral contra- ceptive pill or hormone replacement
therapy (HRT). However, the role of estrogen is also well documented in studies of the
growth of tumors in animals and of human breast cancer cells in culture, and the
established involvement of estrogen in clinical studies has formed the basis for the
successful use of endocrine therapy as a targeted approach to treatment for breast cancer.
Image: Chemical components of personal care products that have been shown to possess
estrogenic activity using assay systems in vitro and in vivo. Estrogenic chemicals are
grouped according to their function in the product.
Insert: The molecular basis of estrogen action. Physiological estrogen or estrogenmimicking compound (E) enters a cell and binds to an intracellular receptor protein (R),
resulting in the release of receptor-interacting proteins (RIP). The estrogen-receptor
complexes dimerize and bind to specific nucleotide sequences in the DNA in the vicinity
of estrogen-regulated genes. RNA polymerase binds to the DNA (POL), as do several
other coactivators of transcription (CO), and this results in regulation of gene expression.
Source: Darbre PD (2011). Personal Care Products and Breast Cancer. Elsevier Science, UK
60
Intro
Food
Epigenome
Method
Implication
Aluminium (7a/10)
Al-compounds in nipple aspirate found
to induce breast tumors, as Al is:
• is a metalloestrogen (enabling
oestrogenic effects)
• transmigrates across cells
• known to interfere with DNA
(micronucleus asssays)
• dermal absorption (e.g. via
anti-transpirants);
• accumulates in biological
fluid (nipple aspirate)
Darbre et al. 2011
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61
The human breast is exposed to aluminium from many sources including diet and personal care
products, but dermal application of aluminium-based antiperspirant salts provides a local longterm source of exposure. Recent measurements have shown that aluminium is present in both
tissue and fat of the human breast but at levels which vary both between breasts and between
tissue samples from the same breast. We have recently found increased levels of aluminium in
noninvasively collected nipple aspirate fluids taken from breast cancer patients (mean 268 +/-28
μg/l) compared with control healthy subjects (mean 131 +/-10 μg/l) providing evidence of raised
aluminium levels in the breast microenvironment when cancer is present. The measurement of
higher levels of aluminium in type I human breast cyst fluids (median 150 μg/l) compared with
human serum (median 6 μg/l) or human milk (median 25 μg/l) warrants further investigation into
any possible role of aluminium in development of this benign breast disease. Emerging evidence
for aluminium in several breast structures now requires biomarkers of aluminium action in order
to ascertain whether the presence of aluminium has any biological impact. To this end, we report
raised levels of proteins that modulate iron homeostasis (ferritin, transferrin) in parallel with
raised aluminium in nipple aspirate fluids in vivo, and we report overexpression of mRNA for
several S100 calcium binding proteins following long-term exposure of MCF-7 human breast
cancer cells in vitro to aluminium chlorhydrate.
It is possible that if levels of iron binding proteins are found to correlate with raised aluminium in
larger repeat studies, that measurement of ferritin and/or transferrin might provide useful
biomarkers in human breast tissue for the existing link between aluminium and iron suggested as
pathogenetically important for human neurodegenerative disorders.
Image: Mean levels of aluminium, ferritin and transferrin in nipple aspirate fluid samples obtained
from women with (Cancer) or without breast cancer and as compared to levels in blood serum or
breast milk.
Source: Darbre PD, Pugazhendhi D, Mannello F. (2011) Aluminium and human breast diseases.
Journal of Inorganic Biochemistry Vol.105:1484-1488
61
Intro
Food
Epigenome
Aluminium
to induce breast tumors, as Al is:
Method
Implication
(7b/10)
approx. 10 μL
• is a metalloestrogen (enabling
oestrogenic effects)
• transmigrates across cells
• known to interfere with DNA
(micronucleus asssays)
• dermal absorption (e.g. via
anti-transpirants);
• accumulates in biological
fluid (nipple aspirate)
Egartner et al. 2013
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62
Source: Ehgartner B, Roth C., Ripper T., Freingruber A., Hohl T. (2013) – die Akte Aluminium.
ARTE, ORF, SRF
62
Intro
Food
Epigenome
Aluminium
Method
Implication
(7c/10)
to induce GCBD:
• GCBD: Gross cystic breast disease most common benign breast disorder,
(7% of Western women)
• antiperspirant formulations are designed
to block apocrine sweat ducts of the
axilla
Fluid obtained from human sweat glands
• apocrine type I
• transudative type II
Manello et al. 2009
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63
Gross cystic breast disease (GCBD) is the most common benign breast disorder, but the molecular
basis of cyst formation remains to be identified. If the use of aluminium-based antiperspirant salts
is involved in the etiology of gross breast cyst formation, it might be expected that aluminium
would be at elevated levels in human breast cyst fluid (BCF). Aluminium was measured by ICPMS in 48 samples of BCF, 30 samples of human blood serum and 45 samples of human breast
milk at different stages of lactation (colostrum, intermediate, mature). The median level of
aluminium in apocrine type I BCF (n = 27, 150 microg l(-1)) was significantly higher than in
transudative type II BCF (n = 21, 32 microg l(-1); P < 0.0001). By comparison, aluminium
measurements gave a median concentration of 6 microg l(-1) in human serum and 25 microg l(-1)
in human breast milk, with no difference between colostrum, intermediate and mature milk.
Levels of aluminium were significantly higher in both types of BCF than in human serum (P <
0.0001). However when compared with human breast milk, aluminium levels were only
significantly higher in apocrine type I BCF (P < 0.0001) and not in transudative type II BCF (P =
0.152). It remains to be identified why such high levels of aluminium were found in the apocrine
type I BCF and from where the aluminium originated. However, if aluminium-based
antiperspirants are found to be the source and to play any causal role in development of breast
cysts, then it might become possible to prevent this common breast disorder.
Image: Median levels of aluminium in human breast gross cyst fluids according to breast gross
cyst subtypes (*P < 0.0001).
Source: Mannello F, Tonti GA, Darbre PD. (2009). Concentration of aluminium in
breast cyst fluids collected from women affected by gross cystic breast disease. J
Appl Toxicol. Vol.29(1):1-6.
63
Intro
Food
Epigenome
Method
Implication
Aluminium (8/10)
Al-induced Neurodegenerative
Diseases:
Al & Blood-Brain-Barrier (BBB)
• Dialysis Encephalopathy Syndrome
(DES)
• Amyotrophic Lateral Sclerosis (ALS)
• Parkinsonism Dementia (PD)
• Alzheimer‘s Disease (AD)
Exley & House, 2011
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64
The brain must expend energy in its ‘unconscious‘ response to an exposure to biologically available
aluminium. There are many examples where ‚biological effect‘ has resulted in aluminium-induced
neurotoxicity and most potently in conditions that have resulted in an aluminium-associated encephalopathy.
However, since aluminium is non-essential and not required by the brain, its biological availability will only
rarely achieve such levels of acuity, and it is more pertinent to consider and investigate the brain‘s response
to much lower though sustained levels of biologically reactive aluminium. This is the level of exposure that
defines the putative role of aluminium in chronic neurodegenerative disease and, though thoroughly
investigated in numerous animal models, the chronic toxicity of aluminium has yet to be addressed
experimentally in humans. The simplest way reduce the Al-burden is by facilitating the urinary excretion of
aluminium through the regular drinking of a silicic acid-rich mineral water over an extended time period.
This will lower the body and brain burden of aluminium, and by doing so will test whether brain aluminium
contributes significantly to chronic neurodegenerative diseases such as Alzheimer‘s and Parkinson‘s.
AD: The main clinical feature of AD is a slowly-developing, relentless dementia characterized by memory
deficit, confusion, inability to focus attention, incontinence, and per- severative behaviors. Neuropathological
hallmarks of AD include cerebral NFTs, amyloid plaques, and granulovacuolar degeneration. Many studies
have shown that NFTs correlate better with disease severity than amyloid plaques.
DES: Al increase in neural cells stimulates Ca2+ uptake, leading to seizures and death
ALS is characterized by progressive motor weakness affecting the limbs and premature death.
PD dementia is a severe and progressive dementia accompanied by extrapyramidal disease.
ALS and parkinsonism dementia often occur together in the same individuals of these populations. Spinal
neurons of ALS/PD-affected Guamanians contain NFTs rich in Al, silicon and Ca2+. Granulovacuolar
degeneration (GVD) occurs in the ALS/PD cortex, substantia nigra, and other subcortical nuclear. There is
evidence that Al induces both NFT formation and GVD, which are also prominent in AD.
Image: A schematic of the possible distribution of aluminium in plasma, the blood- brain barrier (BBB), the
cerebrospinal fluid (CSF), the brain interstitial fluid (BIF), and the cellular and pathological compartments of
the human brain.
Source: Exley C, House ER (2011). Aluminium in the human brain. Monatsh Chem Vol.142: 357-363
Walton JR (2012). Evidence that Ingested Aluminum Additives Contained in Processed Foods and Alum-Treated Drinking
Water are a Major Risk Factor for Alzheimer’s Disease. Current Inorganic Chemistry, Vol. 2: 000-000
64
Intro
Food
Epigenome
Method
Implication
Aluminium (9/10)
Al-compounds & Alzheimer's Disease (AD):
Walton, 2012
• dietary patterns are akin to a grand-scale experiment whereby some individuals
are consuming large quantities of Al
• selective accumulation over
lifetime selective w/n
neurons of the brain
• Al shows affinity to specific
neuronal transporter
proteins
• small amounts needed
to promote AD
Tomljenovic, 2011
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65
The brain is a highly compartmentalized organ exceptionally susceptible to accumulation of metabolic errors. Alzheimer痴
disease (AD) is the most prevalent neurodegenerative disease of the elderly and is characterized by regional specificity of
neural aberrations associated with higher cognitive functions. Aluminum (Al) is the most abundant neurotoxic metal on
earth, widely bioavailable to humans and repeatedly shown to accumulate in AD-susceptible neuronal foci. In spite of this,
the role of Al in AD has been heavily disputed based on the following claims: 1) bioavailable Al cannot enter the brain in
sufficient amounts to cause damage, 2) excess Al is efficiently excreted from the body, and 3) Al accumulation in neurons
is a consequence rather than a cause of neuronal loss. Research, however, reveals that: 1) very small amounts of Al are
needed to produce neurotoxicity and this criterion is satisfied through dietary Al intake, 2) Al sequesters different transport
mechanisms to actively traverse brain barriers, 3) incremental acquisition of small amounts of Al over a lifetime favors its
selective accumulation in brain tissues, and 4) since 1911, experimental evidence has repeatedly demonstrated that chronic
Al intoxication reproduces neuropathological hallmarks of AD. Misconceptions about Al bioavailability may have misled
scientists regarding the significance of Al in the pathogenesis of AD. The hypothesis that Al significantly contributes to AD
is built upon very solid experimental evidence and should not be dismissed. Immediate steps should be taken to lessen
human exposure to Al, which may be the single most aggravating and avoidable factor related to AD.
Image: Major routes of Al transport in and out of the brain: from the blood, Al enters the brain extracellular fluid (ECF)
primarily through the blood brain barrier (BBB) via transferrin-mediated uptake. Some Al in the brain is rapidly effluxed as
Al-citrate by the MCT-transporter. A significant portion of Al is retained in the cellular compartments (nucleus, ER, bound
to ATP or membrane phospholipids).
Inlet: Staging of aged rat (upper row) and aged human (lower row) of hippocampal CA1neurons stained; Stage 0: the entire
cell appears Al-negative and has normal morphology; Stage I: magentanucleolus, no other staining for Al. Stage II:
magenta nucleolus in pink nucleoplasm with visible chromatin; the cytoplasm is blue. Stage III: magenta nucleolus in an
elongated or irregularly shaped purple nucleus.The cytoplasm is blue. Many apical dendrites from this stage onwards have
a serpentine appearance. Stage IV: the magenta staining appears in the elongated nucleus which now shows less structural
detail; the shrunken cytoplasm is still blue. Stage V: purple to magenta staining appears throughout the nucleus and
cytoplasm. Cell shape is distorted and the axon and dendrites are disrupted.
Source: Tomljenovic L. (2011). Aluminum and Alzheimer‘s Disease: After a Century of Controversy, Is there a Plausible
Link? Journal of Alzheimer‘s Disease Vol.23: 567-598.
Walton JR (2012). Cognitive Deterioration and Associated Pathology Induced by Chronic Low-Level Aluminum Ingestion
in a Translational Rat Model Provides an Explanation of Alzheimer‘s Disease, Tests for Susceptibility and Avenues for
Treatment. Journal of Alzheimer‘s Disease Vol.194947: 1-17.
Walton JR (2006). Aluminum in hippocampal neurons from humans with Alzheimer“s disease. NeuroToxicology
Vol.27:385-394
65
Intro
Food
Epigenome
Method
Implication
Aluminium (10/10)
Al-compounds & Macrophagic Myofascitis
(MMF):
• Al(OH)3 used to induce
immune response
• Present in most vaccines
such as Engerix, Hevac,
Tetavax, Tetracoq, Havrix,
Twinrix, etc.
Gherardi er al., 2001
21-Aug-15
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66
Macrophagic myofasciitis (MMF) is an emerging condition of unknown cause,
detected in patients with diffuse arthromyalgias and fatigue, and characterized by
muscle infiltration by granular periodic acid-Schiff's reagent-positive
macrophages and lymphocytes. Intracytoplasmic inclusions have been observed
in macrophages of some patients. To assess their significance, electron
microscopy was performed in 40 consecutive cases and chemical analysis was
done by microanalysis and atomic absorption spectrometry. Inclusions were
constantly detected and corresponded to aluminium hydroxide, an
immunostimulatory compound frequently used as a vaccine adjuvant. A
lymphocytic component was constantly observed in MMF lesions. Serological
tests were compatible with exposure to aluminium hydroxide-containing
vaccines.
Image: Deltoid muscle biopsy (A) tighly packed macrophages intermingled with lymphocytes
(x100); (B) adjacent section of the same showing immuno-localization of macrophage marker
CD68 (x100); (C) adjacent section of the same showing immuno-localization of T-cell marker
CD3 (x100); (D) nodular aggregation of lymphocytes with microvascular neo-angio-genesis
(x70); (E) HLA antigen expression in macrophages & muscle fibers; (F) lzmphocytes stuck to a
granular macrophage (x600).
Insert: Microanalytic Spectral Analysis showing an abnormal presence of Al in muscle tissue
strictly restricted to the area of macrophage infiltration (53 mg Al/g MF)
Source: Gherardi RK, Coquet M, Cherin P, Belec L, Moretto P, Dreyfus PA, Pellissier JF, Chariot P, Authier FJ.(2001).
Macrophagic myofasciitis lesions assess long-term persistence of vaccine-derived aluminium hydroxide in muscle. Brain,
Vol.124(Pt 9): 1821-1831.
66
Intro
Food
Epigenome
Method
Implication
Epigenome - Epigenetics
15-08-21
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67
Intro
Food
Epigenome
Method
Implication
Epigenetics (1/7)
Memory in planarian flatworms
Thompson & McConnell:
• flatworms conditioned to light;
• using electroshocks to induce
learning &
• feeding samples of parental
flatworm to offspring.
Block & McConnell, 1967
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In 1955, Thompson & McConnell conditioned flatworms by pairing a bright light with an electric
shock. After repeating this several times they took away the electric shock, and only exposed
them to the bright light. The flatworms would react to the bright light as if they had been shocked
(conditioning). They found that if they cut the worm in two, and allowed both worms to
regenerate each half would develop the light-shock reaction. In 1962, McConnell extended the
experiment by feeding the trained and ground flatworms to other flatworms. Incredibly these
flatworms learned to associate the bright light with a shock much faster than flatworms who had
not been fed trained worms (epigenetics).
p.54: Ungar wiederholte McConnells experiment. Auch diese lernten die reaktion auf licht
bedeutend schneller als andere würmer, die man mit teilchen nicht trainierter artgenossen gefüttert
hatte. Ein deutlicher zusammenhang zwischen nahrung und information (epigenetik) …. Bei
einigen afrikanischen stämmen soll noch heute der glaube vorherrschen, dass man über die kraft
eines löwen verfügt, wenn man löwenfleisch verzehrt …. Ostertag …. schlägt vor, »lebende
makromoleküle« (DNA) als lebenselixier zu betrachten. Komplexe biopolymere weisen eine
extrem hohe informationsdichte auf (1·E9-mal höher als die technische) – hier koennte das
geheimnis der »informativen« funktion des lebensmittel liegen ….
Regeneration capabilities of flatworms: Planarian has very simple organ systems. It has small
brain and perceptual organs and digestive system which consists of a mouth, pharynx, and an
intestine. However, its morphogenesis is somewhat complicated and mysterious. Planaria has
highly robust regeneration system. When its part of body is cut, each piece of the part regenerates
itself.
Source: Ungar G. (1974): Der molekulare Code des Gedächtnisses. In: Mannheimer Forum.
Studienreihe Boehringer Mannheim; 141-192, p.163
Ostertag W. (1981): Lebende Makromoleküle als Lebens-Elixier. Humata Verlag Harold S.
Blume, Bern.
Block R.A. McConnell J.V. (1967): Classically Conditioned Discrimination in the Planarian,
Dugesia dorotocephala. Nature 215, 1465-1466
http://en.wikipedia.org/wiki/Planaria
68
Intro
Food
Epigenome
Method
Implication
Epigenetics (2/7)
A phenotypic variation
(paramutation):
• same parents;
• same age;
• no mutation in pigmentation;
Image: Jirtle, 2007
…. all mice are genetically IDENTICAL ….
…. but they are epigenetically different !
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69
A study found that an enriched environment can even override genetic mutations in mice
[Waterland & Jirtle 2003]. The scientists looked at the effect of dietary supplements on pregnant
mice with the abnormal "agouti" gene. Agouti mice have yellow coats and are extremely obese,
which predisposes them to cardiovascular disease, diabetes and cancer …. Methyl groups also
inactivate remnants of past viral infections, called transposons. 45% of the human genome is
made up of parasitic transposons. Methylation is nature's way of allowing environmental factors
to tweak gene expression without making permanent mutations, Dr. Jirtle said. Methyl groups
are entirely derived from the foods people eat. And the effect may be good or bad. Maternal
diet during pregnancy is consequently very important, but in ways that are not yet fully
understood.
For his experiment Jirtle chose a mouse that happens to have a transposon right next to the gene
that codes for coat color. The transposon induces the gene to overproduce a protein that turns the
mice pure yellow or mottled yellow and brown. The protein also blocks a feeding control center in
the brain. Yellow mice therefore overeat and tend to develop diabetes and cancer. To see if extra
methylation would affect the mice, the researchers fed the animals a rich supply of methyl groups
in supplements of vitamin B12, folic acid, choline and betaine from sugar beets just before they
got pregnant and through the time of weaning their pups. The methyl groups silenced the
transposon, which in turn affected the adjacent coat color gene. The babies, born a normal
brownish color, had an inherited predisposition to obesity, diabetes and cancer negated by
maternal diet.
Source: http://blog.plantpoisonsandrottenstuff.info/category/vitamins/
Waterland R.A. & Jirtle R.L.(2003). "Transposable Elements: Targets for Early Nutritional
Effects on Epigenetic Gene Regulation." Molectilar and Cell Biology 23(15): 5293-5300.
Randy L. Jirtle & Michael K. Skinner (2007) Environmental epigenomics and disease
susceptibility. Nature Reviews Genetics 8, 253-262
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Epigenetics (3/7)
These transgenic Mice:
• yellow pups develop
obese, cancer & diabetes;
• brown pups are healthy;
Wong, et al. Hum Mol Genet 14:R11, 2005
IJirtle R. 2007
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Gene expression is conditioned by environment: developmental interactions
occur from conception till death - Depends on what environments and what
sequence the organism encounters them.
Epigentic signals can be transmitted to the next generation i.e. display meiotic
stability. Not all epigenetic signals are erased and reprogrammed during
gametogenesis. This partly explains incomplete penetrance and variable
expressivity – not all offsprings are affected (see phenotypic expression of agouti
mice mutants).
Example: mouse agouti locus
Isogenic Avy/a mice range in colour from yellow to black (pseudoagouti)
Darkness proportional to amount of DNA methylation in agouti gene
(complete methylation  black). Transplants’ colour influenced by genetic
mother not surrogate.
Source: http://www.pbs.org/wgbh/nova/sciencenow/3411/02.html
Waterland R.A. & Jirtle R.L.(2003). "Transposable Elements: Targets for Early Nutritional
Effects on Epigenetic Gene Regulation." Molectilar and Cell Biology 23(15): 5293-5300.
Albert H.C. Wong, Irving I. Gottesman and Arturas Petronis (2005) Phenotypic differences in
genetically identical organisms: the epigenetic perspective. Human Molecular Genetics 14:R11R18
70
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Method
Implication
obese, cancer & diabetes;
• brown pups are healthy;
•
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Agouti mothers received methyl-group-rich supplements …. When methyl
groups attach to a gene's DNA, it changes the binding characteristics of
regulatory chromosomal proteins. If the proteins bind too tightly to the gene, the
protein sleeve cannot be removed and the gene cannot be read. Methylating
DNA can silence or modify gene activity …. The mothers who got the methyl
group supplements produced standard, lean, brown mice, even though their
offspring had the same agouti gene as their mothers. The agouti mothers who
didn't get the supplements produced yellow pups, which ate much more than the
brown pups. The yellow pups wound up weighing almost twice as much as their
lean, "pseudo-agouti" counterparts ….
Source: Lipton B. (2005) Biology of Belief. Elite Books, p.70-71
Waterland R.A. & Jirtle R.L.(2003). "Transposable Elements: Targets for Early Nutritional Effects on
Epigenetic Gene Regulation." Molectilar and Cell Biology 23(15): 5293-5300.
Video: http://www.pbs.org/wgbh/nova/sciencenow/3411/02.html
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Method
Implication
obese, cancer & diabetes
• brown pups are healthy
• cause: maternal diet (!)
Ep
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Epigenetics (5/7)
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Feeding the mother with methyl-enriched food supplements …. one can see that
how dramatically the mice shifted the coat color and we get many, many more
brown animals
And that matters because your coat color is a tracer, is an indicator…. of the fact
that you have turned off that gene. This epigenetic fix was also inherited by the
next generation of mice, regardless of what their mothers ate. And when an
environmental toxin was added to the diet instead of nutrients, more yellow
babies were born, doomed to grow fat and sick like their mothers.
Basically, what we eat (our mother / our grandparents ate) affects/ed our gene
expression!
Source: Video: http://www.pbs.org/wgbh/nova/sciencenow/3411/02.html
Waterland R.A. & Jirtle R.L.(2003). "Transposable Elements: Targets for Early Nutritional Effects on
Epigenetic Gene Regulation." Molectilar and Cell Biology 23(15): 5293-5300.
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Implication
Epigenetics (6/7)
Rats & ECD (Paramutation):
• Epigenetic transgenerational
actions of endocrine disruptors
through the male germ line;
• Reduced sperm motility – up to
the 4th generation (F4);
Skinner, 2006
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Michael Skinner von der Washington State University in Pullman, USA setzte schwangere Ratten
Giftstoffen aus, welche ihren Geschlechtshormonhaushalt durcheinanderbrachten. Zusätzlich
verursachten die Giftstoffe in den Keimzellen des männlichen Nachwuchses DNAMethylierungen an verschiedenen Genen und eine verminderte Schwimmfähigkeit der Spermien.
Kreuzte man die männlichen Nachkommen dieser Mütter in der Folge mit unbehandelten
Weibchen, wurde zum Erstaunen der Forscher sowohl das Methylierungsprofil als auch die
reduzierte Spermienmobilität bis in die vierte Generation weitervererbt. Die Bedingungen im
Mutterleib der ersten Generation prägten den Nachwuchs also noch über mehrere Generationen
hinweg. Wie mehrere Studien von Emma Whitelaw von der University of Sydney in Australien
zudem zeigen, ist so eine generationenübergreifende Vererbung epigenetischer Veränderungen
nicht nur auf die männlichen Keimzellen beschränkt, sondern kann auch über Eizellen stattfinden.
Endocrine disruptors have recently been shown to promote an epigenetic transgenerational
phenotype involving a number of disease states (e.g. male infertility). The anti-androgenic
fungicide vinclozolin was found to act transiently at the time of embryonic sex determination to
promote in the F1 generation a spermatogenic cell defect and subfertility in the male. When the
animals were allowed to age up to 1 yr, a number of other disease states developed. This
phenotype was transferred through the male germ line to all subsequent generations analyzed
(F1–F4). The ability of an environmental factor (i.e. endocrine disruptor) to promote an epigenetic
transgenerational phenotype impacts the potential hazards of environmental toxins, mechanisms
of disease etiology, and evolutionary biology. The biological importance of the epigenetic actions
of environmental agents is reviewed in the context of the primordial germ cell and development
of epigenetic transgenerational phenotype
Source: Anway D.M. & Skinner M.K. (2006) Epigenetic Transgenerational Actions of Endocrine
Disruptors. Endocrinology Vol. 147, No. 6 s43-s49
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Method
Implication
Epigenetics (7a/7)
Emotion – the limbic cell (Bookmarking)….
quality of life in womb bookmarks our
susceptibility to diseases later in life;
• newborns “download” huge volumes of
information for their personal development;
• information programmed into
the subconscious mind is
defined as "truth“ (incl. abuses);
• social world hugely influencing
expression of genes (determines
neuronal connections);
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p.156: The fetal and infant nervous system has vast sensory and learning capabilities and a kind of memory
that neuroscientists call implicit memory …. Small creatures with unexpectedly large thoughts"
[Chamberlain 1998] ….
p.158: "For the growing brain the social world supplies the most important experiences influencing the
expression of genes, which determines how neurons connect to one another, which give rise to mental
activity" [Siegel 1999] ….
p.163: The newborn faces a huge challenge – a new environment to cope with, an extremely stressy
situation. Hence, b/w birth and age 6, children “download" an incredible amounts of information they
need to thrive in their environment, thereby establishing the neuronal connections b/w the cortex and the
limbic system ….They do so by carefully observing their environment and download the worldly
wisdom offered by parents directly into their subconscious memory. As a result, their parents' behavior
and beliefs become their own.
p.164: Once programmed i/o the subconscious mind it becomes defined as "truths" (incl. eating habits, verbal
abuses, traumas) that unconsciously shape the behavior and potential of the child through life
(reprogramming via hypnotic state?) …. As we get older, we become less susceptible to outside
programming (however, under extremely emotional events and in an effort to cope with that challenge,
one can relapse into this stage thereby establishing the required connections (emotional) b/w the limbic
system & the cortex, see Sacks p.26-27) …. While most of our senses, such as eyes, ears and nose,
observe the outer world, consciousness resembles a "sense organ" that behaves like a mirror reflecting
back the inner workings of the body's own cellular community; it is an awareness of "self".
p.166: The subconscious mind is like a programmable "hard drive" into which our life experiences are
downloaded and become hardwired stimulus-response behaviors …. When a stimulus is perceived, it will
automatically engage the behavioral response that was learned when the signal was first experienced
(later on our sensors are needed only to evoke an emotional response to environmental stimuli). In fact,
people who realize the automated nature of this playback response frequently admit to the fact that their
"buttons have been pushed" ….
Source: Lipton B. (2005) Biology of Belief. Elite Books
Sacks O. (2008) Musicophilia – Tales of Music and the Brain, 5th ed.. A.A.Knopf, Toronto - CDN
Siegel, D. J. (1999). The Developing Mind: How Relationships and the Brain Interact to Shape Mo We Are.
New York, Guilford - USA
Chamberlain, D. (1998). The Mind of Your Newborn Baby. N.Atlantic Books. Berkeley – USA
74
74
Intro
Food
Epigenome
Method
Implication
Epigenetics (7b/7)
Emotion – the limbic cell (Bookmarking)
• newborns “download” huge volumes of
information for their personal development
• information programmed into the subconscious
mind is defined as "truth“ (incl. abuses);
• social world hugely influencing expression of
genes (determines neuronal connections);
• generates emotions – via controlled release of
regulatory signals (nervous-, endocrine system);
• conscious mind reads the flow of cellular signals
(which comprises the mind of the body);
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p.131: The evolution of the limbic system …. converted the chemical communication signals into
sensations that could be experienced by all of the cells in the community. Our conscious
mind experiences these signals as emotions. The conscious mind not only "reads" the flow of
the cellular coordinating signals that comprise the body's "mind", it can also generate
emotions, which are manifest through the controlled release of regulatory signals by the
nervous system (unfolding EXformation)….
p.132: Candace Pert …. established that the "mind" was not focused in the head, but was
distributed via signal molecules to the whole body (s. also M.W.Ho) …. While proper use of
consciousness can bring health to an ailing body, inappropriate unconscious control of
emotions can easily make a healthy body diseased …. [Pert 1997] ….
p.135: Our responses to environmental stimuli are indeed controlled by perceptions, but not all of
our learned perceptions are accurate. Not all snakes are dangerous! Yes, perception
"controls" biology, but …. perceptions can be true or false. Therefore, it is more accurate to
refer to these perceptions as beliefs. Beliefs control biology
p.167: e.g., if a ball flies t/w your eye …. the subconscious mind, which processes some 20·E6
environmental stimuli per second vs. 40 environmental stimuli interpreted by the conscious
mind in the same second, will cause the eye to blink [Norretranders 1998] ….
Reflex behaviors …. e.g. driving a car at 65km/h on a highway while your conscious mind is fully
engaged in conversation with a passenger …. Through the conditioned learning process,
neural pathways between eliciting stimuli and behavioral responses become hardwired to
ensure a repetitive pattern ("habits") ….
Image: Overview of the information flow through a human being. A so-called organogram. shows
that more information goes in and out of humans than consciousness perceives.
Pert, Candace (1997). Molecules of Emotion: The Science Behind Mind-Body Medicine, New
York
Norretranders T. (1998) The User Illusion Cutting Consciousness Down to Size. Penguin Books,
NY – USA
S. Lehrl and B. Fischer (1985). "Der maximale zentrale Informationsfluss" Grundlagenstudien
aus Kybernetik und Geistenswissenschaji/Humankybernetik 26: 147-154
According to Hans Kuhn (1988), chemist ….biological evolution consists of a series of choices
where an organism relates to its surroundings. These surroundings subject it to pressure, and
i
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Method
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Epigenetics (7c/7)
Emotion – the language of the cell
• the “upper-I” (regime of morality);
5)
• the “I” (regime of reality);
Ps
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• the “IT” (regime of lust);
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Engaging the subconscious in battle is as pointless as kicking the jukebox in the hope that it will
reprogram its play list ….
p.171: Tensions between conscious will power and subconscious programs can result in serious
neurological disorders (movie “Shine”: why we should not challenge the subconscious) …. Most
of us engage in less dramatic battles with our subconscious mind as we try to undo the
programming we received as children ….
i) jede entscheidung bewegt sich im emotionalen rahmen d.h. jede entscheidung muss emotional
ertraeglich sein – nur auf dieser basis kommt der Intellekt zum einsatz;
i) gr. veraenderungen (denk- & verhaltensmuster) muessen sich auf emotionaler Basis
entwickeln;
i) dramatische veraenderungen – tiefe betroffenheit – bedeutet grundlegende veraenderung;
i) intellektueller Impuls (z.b. du sollst nicht rauchen) reicht nicht; erst wenn man die emotionalen,
tieferen bereiche anspricht kann eine veraenderung induziert werden.
Das Über-Ich kann im Freud'schen 3-Instanzen-modell vereinfacht als die moralische instanz /
gewissen angesehen werden und stellt den gegenspieler für die elementaren lusttriebe des ES dar.
Es wird in der frühen kindheit (bis zum 6. LJ) gebildet und enthält die (moralischen) normen und
verinnerlichten wertvorstellungen der kulturellen umgebung, in der das individuum aufwächst
(insbes. die der eltern!). Das Über-Ich entsteht durch angleichen der eigenen person an andere,
mit denen sich dieser mensch identifiziert (introjektion durch die gemeinschaft, gllgemeinheit).
Wenn ein mensch zu denken beginnt, geschieht dies bereits unter dem einfluss des Über-Ichs, und
der darin enthaltenen grundsätzlichen wertvorstellungen. Das Über-Ich fungiert in der
menschlichen psyche als eine kontrollinstanz, deren ziel es ist, durch selbstbeobachtung das
eigene verhalten in uebereinstimmung mit dem idealbild zu bringen. Bei ES-bedingten
abweichungen von diesem ideal wirkt sich das Über-Ich auf den menschen in form des
verspürens von schuldgefühlen aus.
Source: Klussmann R. (2000) Psychotherapie, 3te Auflage. Springer, p.5 & 20-28
http://en.wikipedia.org/wiki/Id,_ego,_and_super-ego
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Epigenome
Method
Implication
Diet (1a/10)
Eastern versus Western Diet
• Local eating habits evolved over centuries / fast food over one decade;
Oldways, 2008
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F.A.Popp lebte einige zeit in China .... Hat dort gelebt wie “gott in Frankreich“ .... und hat in
dieser zeit 5kg abgenommen …. Wie geht das? Weil die nahrung gesund war und weil er wusste
was ihm gut bzw. nicht gut tat ....
p.xl: Das gegenteil passiert wenn jemand in die USA reist und keine zeit für esskultur hat ....
Diese esskultur bringt uns um. Wir leben zwar länger, aber im grunde genommen leben wir nicht
länger sondern wir werden konserviert. Wir sterben langsamer ....
p.14: Amerikaner leben fast ausschliesslich von konserven, chinesen konnten sich das bisher nicht
leisten. sie sind auf frischkost angewiesen …. Es scheint so, als ob konservierungsstoffe nicht
nur die lebensmittel, sondern auch den verbraucher mitkonservieren …. Ein chinese wird im
durchschnitt etwa gleich alt wie ein amerikaner. dennoch haben die chinesen ein deutlich
geringeres risiko, nach dem 50sten lebensjahr unter »zivilisationskrankheiten« wie
kreislaufversagen, krebs, rheuma zu leiden als die gleichaltrigen us-bewohner ….
p.52: So unpraktisch dieser weg zur beurteilung der lebensmittelqualität auch erscheinen mag ….
wir lernen aber daraus erneut, dass »subjektive« komponenten die entscheidende rolle spielen. so
dürfte es vermutlich besser sein, den chinesen im allgemeinen mit reis, den europäer aber mit
weizen zu ernähren, als umgekehrt mit fatalen folgen missionierungsversuche zu unternehmen.
Source: http://www.oldwayspt.org/store/index.php/cPath/5
www.momskitchen.in/articles.php
http://www.isrealli.org/another-reason-to-trash-junk-food/
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Method
Implication
Diet (1b/10)
Western Diet – Olestra
• inhibits absorption of some vitamins (A, D, E, & K);
H
el
p
CSPI, 2009, Wikipedia, 2009
O
Li les
ne tr
(fu a
ll
cl
ip
• sometimes causes underwear staining associated with
"anal leakage“;
)
• may cause abdominal cramping;
Personal enquiry confirmed that Olestra is
currently being used in deep fried products
in a FFR (Salzburg, Getreidegasse
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Olestra (brand name Olean) is a fat substitute that adds no fat, calories, or cholesterol to products;
used in the preparation of high-fat foods such as potato chips, thereby lowering or eliminating
their fat content.
The irony is that it encourage consumers to eat more of the "top of the pyramid" foods due to the
perception of it being more healthy, a paradox resulting in over-consumption thinking that Olestra
allows that without consequence. The FDA was particularly hesitant to approve the product due to
the side effects such as diarrhea and concern for the loss of fat-soluble vitamins.
Chemistry: Normal fats consist of a glycerol molecule with three fatty acid tails attached. Olestra
is synthesized using a sucrose molecule, which can support from six to eight fatty acid chains
arranged radially like an octopus, and is too large to move through the intestinal wall and be
absorbed. Olestra has the same taste and mouthfeel as fat, but since it does not contain glycerol
and the fatty acid tails can not be removed from the sucrose molecule for digestion, it passes
through the digestive system without being absorbed and adds no calories or nutritive value to the
diet. Since it contains fatty acid functional groups, Olestra is able to dissolve lipid-soluble
vitamins such as vitamin D, E, K, & A, along with carotenoids. Fat soluble nutrients consumed
along with Olestra products are excreted along with the undigested Olestra molecules. To
counteract this loss of nutrient, products made with Olestra are fortified with oil soluble vitamins
to compensate for this loss to fecal matter. In 1999, researchers discovered that Olestra helps
facilitate the removal of dioxins from the body, as it apparently binds to dioxins in a manner
similar to that of normal fats. This unexpected side effect may make the substance useful in
treating victims of dioxin poisoning.
Source: http://www.cspinet.org/olestra/11cons.html & http://en.wikipedia.org/wiki/Olestra
Virginia M. (1993) Food – A Source Book, 1st ed. OSU Department of Chemistry
College of New Rochelle New Rochelle, NY – USA
JA Weststrate , KH van het Hof (1994). Sucrose polyester and plasma carotenoid concentrations
in healthy subjects. Am J Clin Nutr 1995 62: 591-597
Seddon J.M.; Ajani U.A.; Sperduto R.D.; Hiller R.; Blair N.; Burton T.C.; Farber M.D.;
Gragoudas E.S.; Haller E.; Miller D.T. (1994). Dietary carotenoids, vitamins A, C, and E, and
advanced age-related macular degeneration. Eye Disease Case-Control Study Group. JAMA
272:1413-1420.
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Method
Implication
Diet (1c/10)
Western Diet – Nutrasweet (Aspartame)
• C14H18N2O5
• health hazard to those born w/
phenylketonuria (PKU;
• acute & chronic toxicity studies in
mice, rats, hamsters & dogs have found
no adverse up to at least 4000 mg/kg
BW/day;
• synergistic effects?
• long-term studies?
Hodgson, 2001
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In 1985, Monsanto bought G.D. Searle and the aspartame business became a separate Monsanto
subsidiary, the NutraSweet Company.
Chemistry: Aspartame is the methyl ester of the dipeptide of the natural amino acids L-aspartic
acid and L-phenylalanine. Under strongly acidic or alkaline conditions, aspartame may generate
methanol by hydrolysis. Under more severe conditions, the peptide bonds are also hydrolyzed,
resulting in the free amino acids.
In certain markets aspartame is manufactured using a genetically modified variation of E. coli.
Upon ingestion, aspartame breaks down into natural residual components, including aspartic acid,
phenylalanine, methanol, and further breakdown products including formaldehyde, formic acid,
and a diketopiperazine. High levels of the naturally-occurring essential amino acid phenylalanine
are a health hazard to those born with phenylketonuria (PKU), a rare inherited disease that
prevents phenylalanine from being properly metabolized.
Source: http://en.wikipedia.org/wiki/Aspartame
Hodgson A.S. (2001). Falsifications and Facts about Aspartame. Cooperative
Extension Service, CTAHR, Hawaii – USA.
Magnuson BA, Burdock GA, Doull J, et al (2007). "Aspartame: a safety evaluation based on
current use levels, regulations, and toxicological and epidemiological studies". Crit. Rev. Toxicol.
37 (8): 629–727
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Method
Implication
Diet (2/10)
Bioaccumulation in the Food Chain
Eastern versus Western Diet
The so-called, four basic foods are
• Grains and cereals;
• Milk and dairy products;
• Meat, fish and poultry;
• Fruit and vegetables;
An industry-oriented approach!
Example: Hg
(s.a. slide 20)
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i) 'Feed the man meat!' (ecologically unsustainable)
i) 'Milk is good for you!' (overload of protein)
i) 'Bread is the stuff of life!' (is not a vegetable, just a filler)
p.146: We are encapsulated by the 'four-foods philosophy'. Yet, many people are allergic to at
least two of these four foods (e.g. milk, dairy products, & grains, cereals). Intolerance and
allergy comes about because of the body's inability to process certain foods properly ....
Undigested food particles enter the bloodstream and wreak havoc throughout the body. These
toxins continue to accumulate in the body, lowering tolerance, wrecking the immune system
and finally evolving into specific disease.
p.148: Grains and cereals …. Symptoms can range from overweight, tiredness, mental illness, to
chronic disease …. Grains are acid-forming in the body. Even when cooked, they are,
comparatively, difficult to digest and can produce abdominal swelling and flatulence. Because
they are a seed, they contain an enzyme inhibitor, which is not easily broken down, even by
cooking …. Wheat in particular, cause deposits of calcium salts in the tissues, leading to
degeneration and hardening of the arteries …. White flour …. can't keep laboratory animals
alive ….
p.151: Milk and dairy products …. Pasteurization destroys the natural enzymes present in raw
milk. Without them milk cannot be properly digested …. Effects to infants (<12 months of
age): gastrointestinal blood loss due to the baby's underdeveloped GIT. Cow's milk is too high
in protein, Na, and K for a baby's immature kidneys - places them under great strain. Anaemia
may develop …. Cow's milk, fed too early …. can damage their digestive systems and render
them allergic, or sensitive, to milk for life ….
p.154: Meat, fish and poultry …. A lot of meat in the diet is particularly bad for allergy sufferers
because it places a greater strain on bodily functions, already overstressed by constant allergic
reactions (bioaccumulation of environmental toxins) ….
p.157: Fruit and vegetables …. the ultimate diet for the onward maintenance of good health, is
one that consists mainly of fresh fruit and vegetables …. For food/chemical allergy sufferers, a
largely vegetarian diet is often the best answer, perhaps supplemented, if tolerance allows, by
a small, irregular quantity of the other basic foods.
Source: Griffiths S. 1996. Allergy overload. HarperCollins (Australia)
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Method
Implication
Diet (3/10)
Bookmarking & sudden change of
diet during the Bengali famine
1943:
• emergency procedures to feed the
needy;
• 110·E6 free meals;
• intolerance to novel food (e.g.
wheat);
• result: still 3·E6 people died;
Wikepedia, 2009
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Das beispiel ist nicht weltfremd: 1943 starben in bengalen drei millionen menschen, weil man
versucht hatte, ihnen ihre gewohnten, aber knapp gewordenen reisvorräte durch weizen zu
ersetzen ….
Auch der verbraucher strebt keineswegs einheitliche kost an .… Die diversität ist es, die er sucht,
ebenso wie er in einem konzert eben nicht nur die ständige wiederholung des kammertons a
geniessen könnte ….
Source; http://en.wikipedia.org/wiki/Bengal_famine_of_1943
http://farm4.static.flickr.com/3022/2599462069_3983e36cfd.jpg?v=0
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Implication
Diet (4/10)
Paramutation - Oeverkalix study
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•exposure to cigarette smoke can lead to a transgenerational
effect but is restricted to boys;
•poor food supply of paternal grandparents was followed by
reduced mortality in grandchildren;
•rich food supply of paternal grandparents was followed by
increased mortality in grandchildren;
•effects last over 2 generations;
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Oeverkalix-studie (unkonventionelle epigenetic): detaillierte aufstellung der
lebensgewohnheiten und todesursachen der grosseltern-generation;
i) systematische langzeitstudie mit 14·E3 kindern vor der pubertaet:
i) einfluss der ernaehrung auf koerpergewicht und gesundheit der nachkommen;
i) grosses nahrungsangebot bei den grossvaetern verkuerzte die lebenserwartung
der enkel (diabetesrisiko stieg an)
i) knappes nahrungsangebot bei den vaetern verrringerte das kardio-vaskulaere
und diabetes-risiko bei den kindern;
i) es hat sich gezeigt das epigenetische praegungen mindestens ueber 2
generationen anhalten koennen;
Source: Bygren, Lars Olov; Kaati, Gunnar; Edvinsson, Sören (2001) Longevity Determined by
Paternal Ancestors' Nutrition during Their Slow Growth Period. Acta Biotheoretica, 49:53-59.
Marcus E Pembrey, Lars Olov Bygren, Gunnar Kaati, Sören Edvinsson, Kate Northstone, Michael
Sjöström, Jean Golding and The ALSPAC Study Team (2006) Sex-specific, male-line
transgenerational responses in humans. Eur J Hum Genet 14: 159-166
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Intro
Food
Epigenome
Method
Implication
Diet (5/10)
Bookmarking – Fetal diet & adult health:
• Rich fetal diet:
i) adjusted to a high level of nutrition in
adult life develop a large phenotype –
better adult conditions = better health
(except at very high levels of nutrition).
• Poor fetal diet:
i) adjusted to poor adult nutrition in adult
life develop a small phenotype
i) in very poor adult conditions they are
expected to be healthier than those with
large phenotypes.
Bateson, et al., 2004
15-08-21
Madl
83
The adult health and likelihood of survival of two groups of individuals with extreme phenotypes
are given for a variety of nutritional environments. For individuals whose early environment has
predicted a high level of nutrition in adult life and who consequently develop a large phenotype,
the better the conditions, the better will be their health except perhaps at very high levels of
nutrition. For individuals whose conditions in fetal life predicted poor adult nutrition and who
develop a small phenotype, the expected outcome is less clear.
In very poor conditions they are expected to be healthier than those with large phenotypes. It
seems plausible that their health would be benefited by some improvements in their nutritional
environment in later life, but these improvements would diminish with further increases in the
nutritional environment. Whether such individuals would be worse off in absolute terms than in a
low nutritional environment, and the slope of the graph eventually becomes negative, is difficult
to assess, but relative to the large phenotype individuals they are expected to be much less
healthy.
Image: The hypothetical relationship between adult health and nutritional level during later
development for two extreme human phenotypes that were initiated by cues received by the fetus.
Source: Bateson P., Barker D., Clutton-Brock T., Deb D., D’Udine B., Foley R.A, Gluckman P.,
Godfrey K., Kirkwood T., Lahr M.M., McNamara J., Metcalfe N.B., Monaghan P., Spencer H.G.
& Sul1 S.E. 2004. Developmental plasticity and human health. Nature 430: 420-421.
83
Intro
Food
Epigenome
Method
Implication
Diet (6/10)
Paramutation - Maternal undernutrition & low birth weight:
• increased risk of obesity;
• increased risk of diabetes;
• increased risk of cardiovascular
disease during adult life;
• increased risk of colon cancer;
Jimenez–Chillaron et al.,2008
15-08-21
Madl
84
"The quality of life in the womb, our temporary home before we were born, programs our
susceptibility to coronary artery disease, stroke, diabetes, obesity and a multitude of other
conditions in later life," …. [Nathanielsz 1999] …. An expectant mother might well
logically reason that what she eats will affect her unborn child. But the evidence is
mounting that not only her children, but her grandchildren and subsequent generations
will be affected by her nutrition. What she eats may not only affect her descendants as
they develop, but potentially throughout their adult lives.
A study published Jimenez–Chillaron et al., indicate that low birth weight is associated
with increased risk of obesity, diabetes and cardiovascular disease during adult life, the
team wanted to know whether such disease risks might be passed on to future
generations. Maternal exposure to glucocorticoids in pregnancy induces hypertension
and/or evidence of insulin resistance, obesity and altered muscle mass as well as
alterations in the hypothalamic–pituitary–adrenal axis in the adult progeny of several
experimental species. When pregnant rats are given restricted diets, their offspring are
smaller at birth; but when the offspring are subsequently given plenty of food they
become more obese than the offspring of mothers given an unrestricted diet; moreover,
for mice that were malnourished in utero, the richer the post-natal diet, the shorter is the
lifespan.
The modern western diet, so full of fats and sugars, could be exerting epigenetic effects
on future generations, positive or negative. Abnormal methylation patterns are a hallmark
of most cancers, including colon, lung, prostate and breast cancer …. The anticancer
properties attributed to many foods can be linked …. to the distinct methylation patterns
of people who eat those foods.
Source: Nathanielsz 1999, Life in the Womb: The Origin of Health and Disease. Ithaca, NY
http://epigenome.eu/en/1,63,0 & http://blog.plantpoisonsandrottenstuff.info/category/vitamins/
Josep C. Jimenez-Chillaron, Elvira Isganaitis, Marika Charalambous, Stephane Gesta, Thais Pentinat-Pelegrin, Ryan R.
Faucette, Jessica P. Otis, Alice Chow, Ruben Diaz, Anne Ferguson-Smith & Mary-Elizabeth Patti (2008) Intergenerational
Transmission of Glucose Intolerance and Obesity by In Utero Undernutrition in Mice. Diabetes 58:460-468.
Melissa Woo1 and Mary-Elizabeth Patti (2008). Diabetes Risk Begins In Utero. Cell Metabolism, Volume 8, Issue 1: 5-7.
84
Intro
Food
Epigenome
Method
Implication
Diet (7/10)
Paramutation - Obese Babies:
•
•
•
•
•
obese mothers give birth to obese babies;
20 genes seem to be involved;
overstimulation of fetal insulin prodctn.;
however, only 1-3% is gene-related;
metabolic related diseases in later life;
e.g.: hormonal disbalance of leptin,
neuropeptides (orexin, etc).
Jimenez–Chillaron et al.,2008
15-08-21
Madl
85
Nach neuen arbeiten spielt neben einer bestehenden stoffwechsel-störung der mutter (z.b.
diabetes) auch ihr gewicht vor und während der schwangerschaft eine wichtige rolle. Dicke
mütter bekommen demnach viel häufiger dicke kinder als normalgewichtige frauen .... Für
das übergewicht der mütter sind verschiedene faktoren ausschlaggebend. Man kennt heutzutage
ca. 20 gene, von denen manche varianten zu einer anfälligkeit für übergewicht führen. Doch
höchstens 1-3% aller personen seien aufgrund eines gendefekts fettleibig .... Bei übergewichtigen
müttern gelange nämlich – wie bei diabetikerinnen – deutlich mehr zucker via nabelschnur in den
blutkreislauf des ungeborenen. Dadurch werde die fötale bauchspeicheldrüse ständig angeregt
insulin herzustellen. Dieses insulin wird mit dem blut ins gehirn des kindes transportiert. Dort
wirkt es über spezielle Rezeptoren, vor allem im hypothalamus. Diese ist unter anderem auch für
die regulation der nahrungsaufnahme zuständig. Wenn nun ständig zu viel insulin im sich
entwickelnden hypothalamus ankommt, wird der sättigungs-sollwert höher eingestellt. Die
einstellung des sollwerts erfolgt im mutterleib. Dies führt zusammen mit der
wachstumsfördernden wirkung des insulins dazu, dass beim fötus einer übergewichtigen frau zu
viele fettdepots angelegt werden. In den fettzellen wird aber das hormon leptin produziert. Dieses
signalisiert im normalfall dem gehirn, wann ausreichend depots angelegt sind. Wenn ein fötus
aber bereits zu viele fettzellen besitzt, produziert er mehr leptin als schlanke ungeborene. Somit
verfügt das sich entwickelnde gehirn sowohl zu viel insulin als auch leptin. Tierversuche deuteten
darauf hin, dass es bei übergewichtigen föten und neugeborenen zu einer gewissen leptinunempfindlichkeit kommt. Dies führe im späteren leben dazu, dass die leptin-signale vom gehirn
weniger gut wahrgenommen und beachtet würden. So könnten sich mehr unnötige fettdepots
ansammeln. Und da insulin und leptin im zusammenspiel mit anderen hormonen wie orexin oder
neuropeptid Y die nahrungsaufnahme und -verwertung regulierten, gerate durch ein überangebot
der beiden erstgenannten hormone das komplexe regulationssystem aus dem gleichgewicht.
Source: übergewichtige babys – mit schwerer hypothek ins leben NZZ 70: 25.3.09
85
Intro
Food
Epigenome
Method
Implication
Diet (8/10)
Paramutation - Starvation in Holland 1944 (compare obesity in Africans)
People exposed to severe
undernutrition in utero –
2nd gen. offspring had ….
• more diabetes;
• 3-fold increase in coronary heart;
disease prevalence;
• more pulmonary disease;
• increased levels of microalbuminuria;
15-08-21
People conceived in famine had ….
• F1-babies w / normal birth weights;
F2-babies weighed 200-300g less;
• higher LDL/HDL cholesterol ratios;
• more likely to be obese;
• suffer from altered coagulation;
• consider th/s psychologically less fit;
• aggerated response to stress - higher
blood pressure rise under stress;
• increased risk of stroke;
Madl
86
The Dutch famine near the end of World War II led to an increased incidence of
schizophrenia in adults who had been food-deprived during the first trimester of
their mothers' pregnancy. Malnourishment among pregnant women in the South
during the Civil War and the Depression has been proposed as an explanation for
the high incidence of stroke among subsequent generations.
Microalbuminuria occurs when the kidney leaks small amounts of albumin into
the urine. In other words, when there is an abnormally high permeability for
albumin in the renal glomerulus.
Weitere beispiele epigenetischer effekte
i) hungerwinter in Holland 1944 (NS-embargo): muetter mit mangelernaehrung
(400-800kcal tagesration) gebaren kinder mit niedrigem geburtsgewicht, diese
gebaren ihrerseits (trotz normaler ernaehrung) wieder untergewichtige kinder;
i) zum zeitpunkt der untersuchung () litten doppelt so oft an herz-kreislauferkrankungen wie ihre altersgenossen;
i) hauefiger brustkrebs und uebergewicht
Source: http://www.hongerwinter.nl/index.php?lang=english
RC Painter, TJ Roseboom, OP Bleker . Prenatal Exposure to the Dutch Famine and
disease in later life: an overview. Reprod Toxicol. 2005 Sep-Oct; 20 (3): 345-352.
http://linkinghub.elsevier.com/retrieve/pii/S0890623805000882
86
Intro
Food
Epigenome
Method
Implication
Diet (9/10)
Bookmarking – BSE & CJD:
• BSE (bovine spongiform encephalopathy;
• CJD (Creutzfeldt-Jakob disease);
• Scrapie (sheep);
All prions-transmissible infectious protein
complexes and induce brain cell
degeneration introduced via food uptake
(epigenetic bookmarking);
Aguzzi et al, 2007
15-08-21
Madl
87
Epigenetic Epidemiology: There is an association of CJD (Creutzfeldt-Jakob disease) and BSE
(bovine spongiform encephalopathy), as well as scrapie in sheep. All are caused by prionstransmissible infectious protein complexes, whose reproduction and reconstruction involve some
type of three-dimensional structural templating.,30 It is thought that BSE is a result of cannibalism
in which faulty industrial practices produced prion-contaminated feed for cattle. There is now
considerable concern that bovine prions may have been passed to humans, resulting in a new form
of CJD. 29
Dementia: It’s an umbrella term for diseases typified by brain cell degeneration beyond what is
expected for a certain age group, due to damage or disease. Dementias that affect the cortex
region of the brain – the outer region that is densely packed with nerve cells, or neurons – include
Alzheimer’s, Parkinson’s, Huntingdon’s and Creutzfeldt-Jakob Disease …. Memory loss and
learning difficulties are the major consequences of these diseases, characterized by abnormal
protein deposits, brain cells dying, and a reduction in new cell growth, which all contribute to
brain circuit damage. Parkinson’s and Huntingdon’s disease affect the regions of the brain just
below the outer cortex, and cause motor symptoms such as involuntary movements.
Image: Reported bovine spongiform encephalopathy (BSE) cases in the UK (blue) and in
countries excluding the UK (orange). Non-UK BSE cases include cases from countries of the
European Union (EU) and outside the EU (CDN, Israel, Liechtenstein, JPN, CH & USA). b)
Reported cases of variant Creutzfeldt–Jakob disease (vCJD) in the UK (blue) and in countries
outside the UK (orange). Non-UK vCJD cases include cases reported in FRA, IRL, ITA, USA,
CDN, Saudi Arabia, JPN, NL, P and ESP. (see the National Creutzfeldt–Jakob Disease
Surveillance Unit web site for vCJD data).
Source: http://epigenome.eu/en/2,58,1112
http://www.cjd.ed.ac.uk/vcjdworld.htm
http://www.rdg.ac.uk/progspecs/pdf06/PFTFTQASSM06.pdf
Jablonka E., Lamb M.J. 2002. The Changing Concept of Epigenetics. Ann. N.Y. Acad. Sci. 981:
82–96
29 Prusiner, S.B. 1998. Prions. Proc. Natl. Acad. Sci. USA 95: 13363–13383.
30 Chernoff, Y.O. 2001. Mutation processes at the protein level: is Lamarckback? Mutat. Res.
488: 39–64.
87
Intro
Food
Epigenome
Method
Implication
Diet (10a/10)
Bookmarking – Food intolerance:
• DNA-methyl. & histone modifs.;
• Hypothalamus-Pituitary-AdrenalAxis (HPA-axis);
• Conditioning;
Garcia et al., 2007
15-08-21
Madl
88
At present, research focuses on the modulation of epigenetic factors regulating the immune
system conditioning…. Such modulators are antisense oligonucleotides, ribozymes and siRNA.
Johansen conducted a study on mice to determine the long-term effects of antihistamines …. 50
mice have been injected with bee venom, a substance to which almost all organisms develop an
allergy upon exposure. Half of the mice were also given 100 micrograms of the antihistamine
Clemastine just before they were given venom, and 100μg
on each of the two days afterwards. After six weeks, the researchers injected the mice with
another dosage of bee venom, and monitored the allergic reactions. They found that mice given
antihistamines reacted more violently to the second venom injection. The findings suggest that the
mice on allergy medication had not developed tolerance to the allergen.
Effects of Conditioning:
p.100: By repeatedly injecting rats with cyclo-phosphamide (a drug that induces nausea &
suppressed the immune system) whenever they drank sweetened water, Ader and Cohen trained
rats to avoid sweet water …. The rats responded by suppressing their immune systems themselves
when faced with what they thought was the same situation again (sweet water & injection, cyclophosphamide had been replaced by a saline solution) ….
p.102: …. All sorts of immune activity can be conditioned, including activation of the
inflammatory response (placebo &) …. (& conditioning) Since the phenomenon of immune
conditioning is already well defined, while the placebo response is not, it would seem preferable
to keep the two terms separate, rather than having two words for the same thing …. Guinea pigs
could be conditioned to associate gentle scratching and inflammation …. Inflammation is …. a
symptom of immune activation, so it seems that immune enhancement can be conditioned as well
as immune suppression.
p.107: Some biologists have suggested that the immune system also functions as a sensory
organ in higher animals, including humans.10 Just as the eyes allow us to detect light waves, so
the immune system, like a sixth sense, enables us to detect the presence of the tiny invaders that
constantly assail us from both within and without.
Source: Isidoro-García M, Dávila-González I, Pascual de Pedro M, Sanz-Lozano C, LorenteToledano F (2007): Interactions between genes and the environment. Epigenetics in allergy.
Allergol Immunopathol (Madr). 35(6):254-8
Evans D. (2004). PLACEBO - Mind Over Matter in Modern Medicine; Harper Collins Publishers;
London - UK
88
Intro
Food
Epigenome
Method
Implication
Diet (10b/10)
Bookmarking – Food intolerance:
• DNA-methylation &
histone modifications;
• HPA-axis;
Griffiths, 1996
15-08-21
Epigenetic conditioning
Madl
89
The alarming number of people who are now suffering from this problem, in varying degrees,
indicates that it is widespread due to the following reasons (incomplete list):
i) Conserved foods: The excessive consumption of refined, pre-packed, tinned, frozen and
artificially-preserved foods, in our Western civilization. The over-consumption of refined
carbohydrates and the almost daily intake of 'fast foods', are aggravating factors.
i) Toxins: Increasing pollution of the environment with chemicals such as fertilizers, insecticides
and hydrocarbons.
i) Overmedication: The vast array of drugs and medication being prescribed daily by doctors for
every conceivable complaint.
The study of ecological illness in the United Kingdom, Europe and the United States, has shown
that food and chemical sensitivities are often multiple. This can make diagnosis complex and
difficult. Most doctors are not generally conversant with the concept that ecological illness can
produce allergies with non-specific symptoms. A wide range of recurring symptoms, resulting in
serious general malaise is often misunderstood.
89
Intro
Food
Epigenome
Method
Implication
Weightloss (1/1)
Yo-Yo-effect:
diet-induced weight loss and rebounce
effect
• there are alterations in the postprandial
release of amylin and pancreatic
polypeptide and,
• changes in levels of leptin, ghrelin,
peptide YY, gastric inhibitory
polypeptide, pancreatic poly-peptide,
amylin, and cholecystokinin,
Mechanistic solution:
• appetite-regulating medications will
probably be required.
Sumithran et al., 2011
21-Aug-15
Madl
90
After weight loss, changes in the circulating levels of several peripheral hormones involved in the
homeostatic regulation of body weight occur. Whether these changes are transient or persist over
time may be important for an understanding of the reasons behind the high rate of weight regain
after diet-induced weight loss.
One year after initial weight reduction, levels of the circulating mediators of appetite that
encourage weight regain after diet-induced weight loss do not revert to the levels recorded before
weight loss. Long-term strategies to counteract this change may be needed to prevent obesity
relapse.
A multitude of hormones, pep- tides, and nutrients are involved in the homeostatic regulation of
body weight, many of which are perturbed after weight loss.
Leptin, an adipocyte hormone, is an indicator of energy stores and acts in the hypothalamus to
reduce food intake and increase energy expenditure
Ghrelin, peptide YY, gastric inhibitory polypeptide, GLP-1, cholecystokinin, pancreatic
polypeptide, and amylin are released from the gastrointestinal tract and pancreas in response to
nutrient intake; all but two inhibit intake. The exceptions are ghrelin, which stimulates hunger,
and gastric inhibitory polypeptide, which may promote energy storage.
Our study shows that after diet-induced weight loss, there are alterations in the postprandial
release of amylin and pancreatic polypeptide and, more important, that changes in levels of leptin,
ghrelin, peptide YY, gastric inhibitory polypeptide, pancreatic poly-peptide, amylin, and
cholecystokinin, Given the number of alterations in appetite-regulating mechanisms that have
been described so far, a combination of medications will probably be required.
Image: Mean (+/-SE) Changes in Weight from Baseline to Week 62. The weight-loss program
was started at week 0 and completed at week 10. ITT denotes intention to treat.
Source: Sumithran P, Prendergast LA, Delbridge E, Purcell K, Shulkes A, Kriketos A, Proietto J. (2011). Long-term
persistence of hormonal adaptations to weight loss. N Engl J Med. Vol.365(17):1597-1604.
90
Intro
Food
Epigenome
Method
Implicaion
Preliminary Conclusion (1/1)
ti l
le
nd
)
–
(1
:1
9:
40
Q
Fo i in
od T
C
n
eat only when hungry;
eat slowly and relax;
don’t eat too many foods at once;
do not mix raw fruits and vegetables;
always eat protein foods last;
undereat whenever possible;
don’t drink with meals;
A
sia
•
•
•
•
•
•
•
M
Eating habits to promote good health:
Griffiths, 1996
15-08-21
Madl
91
Eating habits to promote good health
Eat only when hungry: Hunger should be a comfortable feeling, resulting from the body needing
food for energy, rather than from the ravenous cravings, caused by food allergy.
Eat slowly and relax: Remember, saliva contains digestive enzymes. Thorough chewing
considerably aids digestion and assimilation of food. Food broken down into fine particles by
plenty of chewing, places much less strain on the digestive system.
Eat small meals: It is better to eat five, or six, small meals per day, than three larger ones. If you
eat smaller meals, your digestive system is not overloaded and, thus, operates more efficiently,
nutrient absorption is much better and fat assimilation is less.
Do not eat too many foods at once The fewer foods you eat at one meal, the better. Digestion
and nutrient absorption is far more efficient.
Do not mix raw fruits and vegetables: Both raw fruits and raw vegetables should be eaten
separately. The reason is that totally different enzymes are needed to digest each one.
Always eat protein foods last: Proteins require a generous amount of hydrochloric acid, in the
stomach, to enable the enzymes to break them down effectively. This process takes about twice
as long as that of carbohydrates. When these are eaten, little hydrochloric acid is secreted, as
carbohydrates do not need much for digestion. Accordingly, they tend to pass much quicker into
the duodenum. If carbohydrates are eaten after protein, they are held back in the stomach, by the
protein, and fermentation commences.
Undereat whenever possible: Systematic undereating is the greatest single aid to good health.
Even the best possible diet, eaten to excess, will lead to food intolerances and degenerative
disease. Over indulgence in high protein foods is especially harmful. Light meals lead to better
digestion, greater utilisation of nutrients and, believe it or not, fewer hunger pangs.
Do not drink with meals Although a glass of wine occasionally is harmless, generally, drinking
with meals, or immediately before or after meals, should be avoided. The dilution of essential
hydrochloric acid in the stomach, can have a detrimental effect on efficient digestion and
absorption.
91

Pierre MADL Div. of Material Sciences Dep

Transcription

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