Nutrigenomics:

Molecular nutrition of genetic

variation linked to diet

Ignatius Hapsoro Wirandoko

Dipresentasikan pada Seminar Nasional Healthy Diet for Healthy Life,

How to Eat Healthy Diet that Your Body and Soul Agree
Program Studi Ilmu Gizi Fak Kedokteran Univ. Diponegoro
Semarang, 08 Maret 2009

Nutrigenomics Definition
Analyzing the effects of diet on the activity of on
individuals genes and health and the effect of an
individuals genes on metabolism of dietary chemicals
Diet = nutritional science
Activity of genes = molecular biology
Individual = genetics/genomics
Health = physiology
A systems biology science : Multi - disciplinary
Nutrient is independent variable

Nutrient

Gene Expression

Gene expression is independent variable

Nutrigenetics Definition
Effects of individual genetic variation in
response to nutrient
Any two individuals share 99% of their DNA sequence
Most common form of variation
Single nucleotide polymorphism (SNP)
Changes in single base pair
Occur ~ 1 in every 1000bp of human genome
(~ 3 million in human genome)

SNPs may alter regulation of gene expression,

mRNA processing (splicing, half-life etc) and
protein activities

Molekul mechanisms of
genetic variation Linked diet

Ancestral diet

Selection pressures leading

to metabolic programming,
i.e., SNPs tailor man to
enviroment

Modern diet

Human diseases resulting from

incompatibility between
genetic/metabolic programming
and modren diet

NUTRIGENOMIC ASPECTS OF CELLULAR FUNCTION

Dietary Nutrients
Micronutrients

Macronutrients

Other food components

Transduction of
signal via sensory
mechanisms

Metabolism

Genomics, transcriptomics, proteomics, metabolomics as analytical tools in molecular nutrition

NUTRIGENOMICS

Genomics

Transcriptomics

DNA

mRNA

Sequencing
and Genotyping

Pattens of
Gene expression

Proteomics

Protein

Metabolomics

Metabolites

Synthesis and Structure Profile and Fuction

of Proteins
Of metabolites

Examples of Nutrient Interatcions with Genotype That

Have Implications for Human Health

Gene
MTHFR
APOE
APOA 1
GPX4
HFE

SNP/Isoform
C677T
E2+ , E3+ , E4
-75 (G/A)
3 UTR
C282Y, H63D, S65C

Nutrient
Folate, alcohol
- 3 PUFA
PUFA
Selenium
Iron

Nutrigenetics
Genetic variation (SNP) may contribute to disease
differentials
Several alterations will be diet responsive and can
be rendered harmless
Challenge
Defining the right diet for the right population
Tailoring dietary recommendation based on genetic when
appropriate

THE HEALTH PENDULUM

Susceptibility
SNP1
SNP2
Poor
Nutrition
In utero
Food
Component I

Smoking

Protective
SNP1

Good
Nutrition
In utero

Health
pendulum

Food
Component 2

Physical
activity

Time

Health

Disease

GENETIC BUFFERING UNDERPINS NUTRIGENOMIC RELATIONSHIPS

Iron

Iron regulatory protein 1 and 2

Carbohydrates
i.e., glucose

Sterol regulatory element binding protein

Upstream stimulatory factor
Carbohydrate response element binding protein
Zinc

Metal responsive transcription factor

Constituvenly active receptor

Pregnane X receptor

Vitamin D

VDR

Nutrient ligand

Bioflavonoids

Estrogen receptors
Nuclear factor xB

Vitamin A

Xenobiotics

RAR
RXR

Trancription factor

Protein &
amino acid

CCAAT/enhancer-biding protein

Cholesterol

Calcineurin/nuclear factor of activated T cells

Fatty acids

Calcium

Liver X receptor
Farnesoid X receptor
Pregnane X receptor

Vitamin E

Transciption factors and their

Component SNPs contribute to
The mosaic of nutrigenomic effects
That modify phenotype, and
Contribute to human individuality

Sterol regulatory element biding protein

Hepatocyte nuclear factor
Carbohydrate response element biding protein
Peroxisome proliferator activated receptor
Liver X receptor
Modifies gene expression via signal transduction pathways
Pregnane X receptor

PHENOTYPIC STABILITY
Health
Reproductive efficiency
Enhanced competitiveness

Natural selection acts to

promote a robust phenotype in
the face of nutrient variability.
Genetic buffering confers
stability and is achieved via
interactions between gene loci,
nutrient and genes, biologically
active nutrients and the
metabolome, and nutrients with
nutrients. Other buffering
mechanisms include gene
duplication, a complex
regulatory mesh of epistatic
gene interactions, and proteinprotein interactions that lead to
molecular stability

A more robust
cellular integrity

Stochastric variables in the external enviroment:

i.e.,avaviability of food nutrient, and influence of
mutagenic processes,
are subject to genetic
buffering as a mechanism
to impprove phenotypic
stability

Desease
Reproductive inefficiency
Reduced competitiveness

A lessrobust
cellular integrity

PHENOTYPIC INSTABILITY
The Balances between phenotypic outcomes with respect to nutrition and
genetic buffering

Important micronutrientgene interactions, with particular reference to the effect of

certain vitamins and minerals on the genomic machinery and/or gene product.
Some Important MicronutrientGene Interactions
Dietary
Component
Retinoic acid
(vitamin A)

Background
Information

Effect on Genomic Machinery

and/or Gene Product

RXR forms homodimers and

heterodimers with vitamin D,
PPAR, thyroid hormone, and
COUP receptors
Oxidative DNA damage in vitamin
C depletion (formation of 8-hydroxyguanine)

Binds either RXR or RAR nuclear retionoid receptor and enhances transcription,
although in absence of
retinoic acid, heterodimers repress gene expression

Pyridoxal
Phosphate
(vitamin B6)

Modulates responsiveness of
steroid hormone receptor

Attenuates transcription

Riboflavin
(vitamin B2)

Flavin cofactor for 5,10MTHFR

May interact with cellular folate to influence elaboration of DNA (1-C unit from
folate donated to thymine)

Folic acid

Provides 1-C unit for purine, pyrimidine, and methyl groups

May modulate both expression of DNA via CpG methylation pattern and
elaboration of DNA via provision of thymine. If 1-C shortage, uracil is
misincorporated and DNA becomes unstable

Vitamin D

Vitamin D receptor forms a heterodimer with RXR

Enhances transcription of calcium binding proteins

Vitamin K

Growth arrest specific gene 6 product contains -carboxyglutamate

residues

Regulates apoptosis, but it does not interact directly with genomic machinery

-Tocopherol
(vitamin E)

Antioxidant properties. Ameliorates damage to DNA from excess

iron. Induces two signal
transduction pathways that act at several genes, but also acts
independent of these two pathways
Critical for intracellular signaling

Protects genomic machinery from freeradical damage. Alters activity of protein

kinase C and phospotidylinositol 3-kinase. This in turn regulates the expression
of several genes . Also acts
on genes independent of these kinases
Increased transcription of c-fos, c-jun,c-myc

Iron

During deficiency, iron-regulatory protein binds mRNA and promotes

synthesis of transferring receptor protein while ferritin
production is repressed. The net effect is to increase iron utilization

Enhances transcription of metallothionein and translation of ferritin

Magnesium

Required for nucleic acid polymerase enzyme activity

Maintains fidelity of the DNA blueprint

Ascorbic acid
(vitamin C)

Calcium

Potassium

Enhances transcription of procollagen and translation of lysyloxidase

Influences transcription of aldosterone synthase

Selenium

Selenocysteine residue in glutathione peroxidase provides

antioxidant properties

Helps prevent free radical damage to genome

Zinc

Structural motif of zinc finger transcription factors

Augments transcription factor binding

Analytical techniques and potential applications of

transcriptomics in the fileds of free-radical research
TRANSCIPTOMICS

APPLICATIONS
Screening and development of new
antioxidants
Assessing potential effects of
antioxidants
Defining biomarkers of oxidative stress
Evaluating the bioavailability of
antioxidants
Studying redox sensitive signal
transduction pathways

TECHNIQUES
Differential display
cDNA arrays and Gene chips
Serial Analysis of Gene Expression
RT-PCR
Northern blotting

Leading edge Laboratory Tools;

DNA micro arrays
Protein chips
Large scale genomics and proteomic investigations
monitoring of the expression of thousands of
genes in response to diets
how nutrients modify;
- cancer risk
- chronic disease
- aging
most human disease are largely
avoidable by lifesyle changes
Nutrigenomics at the
- forefront of preventive
medicine
- special emphasis on the
gene regulatory activity of
- antioxidants
- phytochemicals
- micronutrients

Free
radikal

Mechanism of selenium as on evolutionary

pressure on gametogenesis
2 mol glutathione (GSH)

Radical generated
Lipid peroxides

NADP+
Glutathione reductase
NADPH

1 mol reduced glutathione (GSSG)

Glutathione peroxidase
enzyme protein with a
selenocysteine residu at
the catalytic site

CH2

H3N CH

C=0

SeH

S-Adenosylhomocysteine Homocysteine
S-Adenosylmethionine
methionine
Genomic
methyiations

B12

5-Methylenetetrahydrofolate

Methyionine
synthase

Equlibrium in
favor of 677C
allele

C667T-MTHFR one carbon flux

B2

Methyionine biosynthesis

Equlibrium in
favor of 677T
allele

Pertubations may increase homocysteine

And hence vascular disease. They may also
Influence DNA methylation
Patterns and gene expression
Homocysteine is also
5, 10-Methylenetetrahydrofolate
Considernet to be embryotoxic

dUMP
Thymidylate synhase
dTMP
Nucleotide biosynthesis and the elaboration of DNA
Pertubations may influence embryogenesis; inadequate folate due to a poor diet and 677MTHFR might lead to uracil misincorparation in DNA, genomic instability, and loss of the
developing embryo. It may also promote cancer

Contemporary selection pressure from periconceptional

folate supplements

Schematic of vitamin A and gene regulation

Micronutrients that act directly or indirectly as

antioxidants or influence DNA expression
Vitamin
A

Vitamin
C

Vitamin
B12

Vitamin
B6

Vitamin
E

Vitamin
B3

Folic
acid

Vitamin
B2

Vitamin
D

Zn,Se,Fe
Mg, Cu

Antioxidants evolutions & Human Health

Threat and management of

deleterious radicals generated
by cellular respiration

Membrane Damage
Free
radicals
+
O2

Mitochhondrial
DNA Damage

l
ica
ad
e r gy
xid er
ro en
pe P
Su AT

Superoxide
dismutase

H2O2

Catalase

Nuclear DNA Damage

O2 + Glucose

H2O and
O2

Homocyteine : genetic and nutritional

factors
MTHFR - Homocyteine
Oxidative stress
Homosisience
Metionin
(Borto & Yang,2000)

Reduce NO
Reduce tetrahydro
biopterin
Metionin
sintase

Low methylation
5 metilTHF
5,10 metilen THF

MTHFR:
C677C (normal)
C677T (akt rendah)

Homocystein and modern society

various mechanisms involved in the deleterious actions of homocysteine

upon cellular processes.

Cellular genomic and nongenomic effects of isoflavones. The effects differ according to the
type of tissue and the number of estrogen receptors within that tissue. The effect on reproductive tissue
is of particular interest and may influence reproductive efficiency.

Causes of Metabolic Syndrome

Stress

Pollution

Food

Second hand smoke

Genetic
Inheritance

Lack of
Exercise

Various Factors Cause Metabolic Stress

Oxidative
Activities

Toxine
Cholesterol

Diabetes Bacteria

Gene

Germ

Lack of
enzyme

Enviroment
INSULIN RESISTANCE

Raised blood lipids

Production of
Oxidant molecules

Acute phase
protein

Fever

Glucose Synthesis

Effect of
cytokines TNF,
IL 1 and IL6

Appetite
Loss and
lethargy

Plasma copper
Plasma Zn
Plasma Iron
Loss of lean
Tissue and
fat

Increased urinary
Nitrogen sulphur
And mineral losses

How Does Abdominal Obesity Cause

Insulin Resistance
Fat proliferates abnormally (OBESITY)
chytokines

chytokines

Chronic inflammation develops

Metabolic Syndrome
Health Destroyer
A collection of metabolic risk factors that accelerate the
onset of diabetes, heart disease, stroke and certain
cancers.

Adipose tissue expands

Proinflammatory
Cytokines Released
Glucose Uptake
Decreases

Pancreas Increases
Insulin Production
Hyperinsulinemia

Blood Glucose Levels

Increase
Hyperglycermia

Triglycerides Released to
Blood Stream
Cardiovascular Disease

OXIDATIVE STRESS

O2 = dangeraous friend (a free radical)

evolution
as the terminal electron acceptor for respiration biradical ;
Others : - SUPEROXIDE ANION/ HYDROL RADICALS
- oxidative
- metabolism, and energy production
- ionizing radiations
endowed with a higher chemical reactivity
involued in - regulation of signal transduction
- gene expression,
- activation of receptors,
- nuclear trancription factors,
- oxidative damage to cell components
- antimicrobial and cytotoxic action of immune
system cells neutrophils and macrophges in
aging &age related degenerative diseases

Oxidative stress can lead to cell and tissue injury

NITRIC OXIDE (NO)

Free radical generated by Nitric oxide synthase (NOS)
modulates physiological responses in the circulation
e.g.- vasodilatation (eNOS)
- signaling in the brain (nNOS)
During inflamation : 1/3 isoenzyme is induced (iNOS)
everproduction of NO tissue damage
- + superoxida anion a strong oxidant : peroxynitrite
Oxidation of
- lipid
- protein
- DNA by peroxynitrite tissue injury

ROS
NOS

redox regulation of cell functions

Oxidative stress as a major upstream component in

- the signaling cascade (in inflamation responses)
- stimulation of adhesion molecule, and
- chemo attractant production
H2O2 decomposes in the presence of transition metals to the
highly reactive hydroxyl radical by 2 major reactive
- hydrogen abstraction and addition
Oxidative damage to:
- lifoid
- sugar
- nucleic acid

H2O2 : an important signaling molecul

activate NFKB (transcription factor in
inflammatory responses)
Low concentration :
- regulated cell signalling
- stimulates cellprofiferation
High concentration :
triggers apoptosis necrosis
Free radicals
Secondary ; most cases
Causal
A Delicate balance : oxidands antioxidants
proper balance healthy aging

Oxidative stress
1)Redox status

the degree to which a cells components in the oxidized state

the reducing environment inside cells helps to prevent
oxidative damage
maintained by (remove ROS)
- oxidative metabolism
- the action of antioxidant enzymes,
- superoxide dismutase
- catalase
- selenium dependent glutathione
reductase
- glutathione hydroperoxidase
- thioredoxin hydroperoxidase
- substances glutathione thioredoxin, vitamin E, C.

2) Depletion of antioxidants

Index of oxidative stress

- Thiol redox status
- GSSG/ GSH ratio (Glutathione disulfide/ glutathione)
- redox couples ratio
- NADPH/NADP
- NADH/ NAD
- Thioredoxin reduced/ thioredoxin oxidized
- Dihydrolipoic acid/ lipoic acid
- lactate/ pyruvate
Energy status of the cell
(ratio ATP/ ADP + AMP)

Current hypotheses: How oxidants antioxidants modulate ?

lowering oxidative stress cell and tissue fuction can have a health
benefit.
Can be - over produced free radicals
- natural antioxidant system defenses weakened
oxidative injury - heart disease
- cancer
- neurodegenerative
disorders
Oxidation of human LDL : early step in the progression and
eventual development of atherosclerosis
Oxidative DNA damage
initiate carcinogenesis
Environmental source of ROS oxidative stress disease
- UV radiation
- Ozon
- Cigarette smoke
- others

FROM
EPIDEMIOLOGICAL STUDIES : antioxidant status (vit C, E)
scientific evidence
Clinical - prevention
- treatment

~ risk of several disease

- Cataract
- Cancer
- Neurodegenerative disorder
- Rheumatoid arthritis
- DM

As - a primary cause
- a secondary complication in many disorders
- inflamatory bowel disease
- retinal ischemic
- CVD and restenosis
- AIDS
- adult respiratory distress syndrome
- stroke
- Parkinsons disease
- Al zheimers disease

Major natural
antioxidant enzyme/ substances (in
foods & beverage)
- vit E, A, C
- flavonoids
- polyphenols
- caretenoids
- lipoic acid
- coenzyme Q10
- carnitine
- other micro nutrients

Trauma/infection/burn
Immune system activation

Immuno
nutrition

Pro-inflammatory cytokines

oxidants

Pathogen
killing

Antioxidant
defence

Tissue
damage

Creation of a
hostile enviroment

Feedback
Systems
IL10, Heat
Shock proteins

T and B Cells
Glucose
Glutamine

Nutrient
Release from
Host tissues

Appetite loss

Sulphur
amino
acids

Glutathione
Synthesis
Antioxidant
defences
strenghened

Methionine
Homocysteine
Vit B6
Cysteine

Oxidants

Vit E
Reduced

Vit E
oxidised

Dehydro
ascorbic
acid
Ascorbic
acid

Glutathione
GSH
Glutathioner
eductase
Riboflavin
Glutathione
GSSG

Inflammatory stimuli
LPS, Oxidants, stress

Transciption
factors

AP1

Cell
Proliferation

NFKB

IL2

Acute
Phase
protein

GSH
synthesis

Adhesion
molecules
IL1,
IL6,
IL8,
TNF

HIV
replication

Antioxidants as free-radical scavengers, metal chelators, and redox signaling molecules

both prevention of oxidative damage towards lipids, protein, and DNA as well as redox
signaling contributes to their beneficial effects.

Antioxidants

Free Radical Scavengers

Metal Chelators

Preventions of Oxidative
Damage towards Lipids
Proteins and DNA

Redox Signalling
Molecules

Antiageing, Antiatherogenic, Anticarcinogenic,

Immunomodulatory, Neuroprotective Effects

Molecular mechanisme for the anti-atherogenic

activity of VE
LDL oxidation
Smooth muscle
Cell proliferation

Scavenger receptor
expression
Inhibitory
Effect of
Vitamin E on

Platelet adhesion
And-aggregation

Nitric oxide and

Cytokine production
Cell adhesion protein
expression

Cell receptors, cellular key enzymes, and transcription factors as molecular targets of oxidants
and antioxidants

Receptors

Phosphatase
Kinases

Transcription
Factors

Oxidants

Antioxidants
Gene Expression

Protein levels

Enzyme Activity

NUTRIGENOMIC

Pangan - GIZI
(anugerah)

KEBODOHAN
(logos)

BIOTEKNOLOGI
Rekayasa genetika
pangan

KEARIFAN
LOKAL

KESERAKAHA
N (eros)

Kanker
(Musibah)

GLOBALISASI

Perilaku
GAYA
HIDUP
Pola/kebiasaan
makan
Rokok, alkohol
Sedentary (obeis)

KANKER

LINGK

Pangan
- Genotoksik/ pro kanker
- Anti kanker
-

Olah
Simpan
BTP
Plastik

GLOBALISASI

- Kontaminan
- Pestisida
- Limbah

Fenotipe Sehat

Fenotipe Sakit

Ekspresi gen/ fenomena

epigenetik
Uji in
Vitro
RISET
EKOLOGI

UJI
KLINIS

RISET
EPIDEMIK

Uji
Hewan

Fakta Epidemiologis
Kashmir : Ca. Oesofagus ~ pengolahan teh + garam
Skandinavia : Cancer lambung & colon ~ daging merah
Migran Jepang : kacang cycad
Mesir : Cancer hati ~ bijian disimpan
Kaukasus : Cancer payudara ~ lemak
Ceko-Polandia : Lemak >< kubis
China : teh hijau, bumbu/ rempah cara masak singkat

PANGAN KARCINOGENIC
Alamiah :

hidrazin
safrole
estragole
psoralen

Geno Toksik

Buatan/ perilaku
manusia
:
prose Simpan
: Aflatoksin, Patulin, Citrinin
s

olah : panas tinggi (goreng, bakar)

aditif pangan etanol

Asupan :

PAH
HAA
NOC

sacharin
karamel
furyl furamid
pewarna azo
nitrat (III, V)

residu minyak goreng& Lemak trans (peroksida lipid)

pengasapan langsung
garam/ pengasinan
Energi (+ OR minimal)
Alkohol berlebih
ROS endogen

KONTAMINAN Lingkungan Pangan

(Via: mata rantai pangan)

Antropogenic environtment pollutant

Mutagenik - Karsinogenik
Polutan organik
PCB (PCDD, PCDF, VOX, Pestisida)
Polutan anorganik
Nitrat (III, V)
Benzo [a] pyrene
Pestisida:
Khususnya organochlorin:
DDT,Chlordane,lindane,DDE,Aldrin
Plastik-styrofoam kemasan (vynil-chlorida)
Benzene
Dioxin
Organohalogen votatil air PDAM
Logam berat; Pb, Ni, As, Cr

Reparasi
SEL

Respons
Radang

Metabolisme
Karsinogen

KOMPONEN
BIOAKTIF
PANGAN

Siklus SEL

Kematian Sel
Terprogram

Regulasi
Hormonal

Diferensiasi

Cegah terjadi
Hambat perjalanan keganasan
Halangi kekambuhan
Gambar : Modulasi Komponen pangan pd Sel Kanker

HANAHAN & WEINBERG

Mandiri signal tumbuh
Insensitif signal hambat tumbuh
Hindar apoptosis
Replikasi tak terbatas
Angiogenesis
Invasi - metastosis

2001 : proyek genom manusia tuntas

penggunaan dalam
riset gizi :
- genomik
- transkriptomik
- proteomik
- metabolomik

nutrigenomi
k

era post
genomik

Lokasi sel
target

Biomarker

Tahapan
Spesifik

Efek spesifik

Dapat dipantau
dipantau
Dapat
adanya perubahan
perubahan
adanya
risiko terhadap
terhadap respon
respon
risiko
intervensi gizi
gizi
intervensi

MEKANISME MOLEKULER
DIET ANTI KANKER
Aktivasi antioksidan

pembersihan radikal bebas

reduksi stres-oksidatif
pengurangan nitrasi,nitrisasi)
pencegahan ikatan DNA

Hambat proliferasi sel

induksi diferensi sel
hambat ekspresi onkogen, induksi ekspresi gen penekan
tumor
induksi henti siklus sel dan kematian sel terprogram
Induksi enzim & peningkatan detoksifikasi:
(enzim fase III, GPX, SOD)
Hambat enzim (COX-2, iNOS, Xanthine oksidase, enzim fox I)

anti pembentukan p. darah baru

hambat adhesi sel (lengket) & invasi
regulasi metabolism H. steroid & estrogen
aktivasi anibakteri-virus

VARIASI DIIT & FAKTOR GENETIK

Respon terhadap intervensi diit
Diit bersifat individual (Personalisasi diit)
~ variasi ekspresi gen :
protein transport
reseptor
enzim katabolis
Penanda biologis
perubahan fenotipe :
proteomic
metabolomic
Mis: aktivitas dehydrogenese alkohol Kaukasus
> Jepang

DIIT BERBASIS TARGET MOLEKULER

Signal
Antitumbuh

flavonoid buah sayur

n.3. FA : EPA, DHA ikan
resveratrol anggur
Vit A, Vit D

Replikasi tak
terbatas

Retinoid sayur buah

EGCG teh hijau
Curcumin
Vit D

Invasi metatase
Katekin
EGCG the hijau + hitam

Regulasi pembelahan

sel

genistein (isoflavon),
fitoestrogen kedele

Apoptosis

resveratrol anggur merah

lyeopere teh
carotene sayur
allyl sulfur bawang putih
caffeic acid, ester propolis
curcumin temu lawak,madu,

Angiogenesis

Katekin teh hijau

EGCG teh hijau
Resveratrol
n-3Fa, EPA, DHA

ANTI Oksidan
Et, Vitamin C
Caroten
Se
EGCG
Quercetin
Genestein
Taxifolin

ANTI Radang

n-3, EPA DHA minyak ikan

Vit A, Vit E
Bromelein
Curcumin
Resveratrol
Quescetin
EGCG

Detoksifikasi
Enzim xenobiotik : Glukosinolat brocoli
Regulasi
Epigenik : - Folat
- Vit B, 12, B2, B6, methionin
- Zn, Se
- Retinoid acid

KHEMOPREVENSI KANKER

Mikronutrient : Vit A, D, E, C, folat, Se

Komponen bioaktif :
Carotene (..)
Lutein
Lycopene

Carotenoid :

Fenolic :

Fenolic acid
Flavonoids
Stilbene
Tannin
Coumarin

Organosulfur :

- Flavonols (Quercetin)
- Flavones (Apigenin)
- Flavanols (Catechin)
- Flavanone (Naringetin)
- Anthocyanidine (Cyanidin)
- Isoflavonoid (Genistein)

Isotiosionat
Indole
sulfur CLA
: sulfida
Alyl
Makronutriet : omega 3,
spingolipid,
Serat

PREVENSI (Lain)
Intensif penggunaan fitokimia

buah
sayuran
biji utuh
serat
produk (ikan, kedele)
susu rendah lemak

kontrol BB, cegah obesitas

Olah raga/ latihan minimal 30 menit
kurangi makan (goreng, bakar/grill, asap, asin)
kurangi lemak jenuh, tak jenuh trans) maks 25%
Stop rokok, minum alkohol minimal

KHEMOPREVENSI DIIT & TARGET MOLEKULER

Mekanisme
Hambat tangkapan

Target Molekuler

Khemoprev. Diit

As. Empedu

Kalsium

Sitokrom P450s

-PE ITC
-Indol -3- carbinol
-Isoflavon

Karsinogen
Hambat aktivasi karsiongen

- PG Synthase
Hydroperoksidase

Curcumin

Slipoxygenase
- As. empedu

-Urosdial

Dexoksifikasi karsinogen

GSH/ GST

NAC bisulfida

Cegah ikat karsinogen-DNA

Sitokran P450s

Katekin

Luas + tingkatan Reparasi DNA

ADP riboxyl transferete

NAC, Protease, Inhibition

Modulasi hormon

- Reseptor estroge

-Isoflavon

Aktivitas fc tumbuh

- Steroid 5 reductose

-Katekin

- IGF.1

-Isoflavon,,Likopen

- AP-1

-Retinoid

- PPARs

MEKANISME DIET (lanjutan)

Hambat aktivitas onkogen

FP transferase

Limonen, DHEA

Hambat metabolisme poliamin

ODC induksi

Retinoids, curcumin, katekin

Induksi diferensiasi terminal

TGF-

Retinoids, vit D nofloam

Restorasi respons imun

TNK limfosil sel langerhons

Selenium katekin

Reduksi inflamasi

NF.KB

EGCG, resveratrol, curcumin

Hambat prod ekosanoid

Cycloxygenne & lipoxygenne

Curcumin resveratrol EPA, DHA,

Katekin

Akeselerasi komunikasi inter sel

Connexin 43

Lycopene retinoids

Induksi Apoptosis

- TGF
- Rosfarelisasi

-Retinoid isoflavon vit D

- Arachidonic Acid

-Retinoic acid

- Caspase

-Retinoids

Induksi senesens

Telomerase

Vit D retinoids

Hambat angiogenesis

FGF receptor

Isoflavon restinoid

-Penillyl alcohol limonen, DHEA

Tyronin kinase
Tranmodulin

Koreksi imbalansi metilasi DNA

Cp6 island metilasi

Asam folat

Hmbt defradesia membran basal

Collagenase IV

Proteese inhibisi

Hambat sintesa DNA

G.6.P dehydrogenase

DHEA

MEMERANGI KANKER
Piramida Pedoman Makan

AICR

keberagaman sumber pangan + proporsi harian

Pembatasan asupan
- Energi
- Lemak
- Gula sederhana

tinggi asupan
- buah-sayur
- karbohidart komplek
- serat

Lemak

- n-3
- FA

Keseimbangan Energi Positif

- gagal regulasi homeostatis (proliferasi, voskularisasi)
- ritme metabolisme stress oksidatif/ internal
- efek biogenetik E-radang-kanker

Tenets of Nutrigenomics
1.Improper diets are risk factors for disease
2.Dietary chemicals alter gene expression and/or
genome structure
3.Influence of diet on health depends upon an
individuals genetic make up
4.Genes regulated by diet play a role in chronic
diseases
5.Personalized nutrition diets based upon
genotype, nutritional requirements and status
prevents and mitigates chronic disease