TERAPI GIZI ANTI-INFLAMASI

PADA PENYAKIT DEGENERATIF

ABDULLAH FIRMANSAH, dr, SpGK, MKes

DF CLINIC
SANTOSA BANDUNG CENTRAL INTERNATIONAL HOSPITAL
Type 2 diabetes: a global call to action
Type 2 diabetes accounts for 85–95% of diabetes cases
333 million
350

300
Global prevalence of
diabetes (millions)

250

200
150 million
150

100

50 30 million

0
1985 2000 2025
Year

http://www.idf.org/home/
 Natural History of Type 2 Diabetes
Genetics
Environment Onset of
Complications
• nutrition diabetes
• obesity
• exercise Disability
Impaired
glucose Ongoing
tolerance hyperglycemia Death

Retinopathy Blindness
Insulin resistance
Nephropathy Renal failure
Hyperinsulinemia
Hypertension Neuropathy
Decreased HDL-C Coronary disease
Increased TG Atherosclerosis LE amputation
 Obesity is a key driver of the diabetes
epidemic

• 50–65% of the general

population are obese or
overweight1
• The risk of developing type 2
diabetes increases with
increasing weight2
• It is estimated that half of all
diabetes cases would be
eliminated if weight gain
could be prevented3

1http://www.idf.org/home/; 2Mokdad AH, et al. JAMA 2003; 289:76–79.

3Knowler WC, et al. N Engl J Med 2002; 346:393–403.
 Despite falling CHD mortality rates,
diabetes increases the risk of CHD
Factors  CHD deaths Factors  CHD deaths
include  smoking, include diabetes and
cholesterol, and BP and obesity
20,000 changes in treatments
Deaths prevented or postponed

-20,000
in 2000

-40,000

-60,000

-80,000

-100,000
Data from England and Wales between 1981 and 2000 in men and women aged 35–84 years
There were 68,230 fewer CHD deaths than expected from baseline mortality rates in 1981

Unal B, et al. Circulation 2004; 109:1101–1107.

 Type 2 diabetes is associated with
serious complications
Stroke
Diabetic 2- to 4-fold increase in
cardiovascular mortality
Retinopathy and stroke5
Leading cause
of blindness
in adults1,2 Cardiovascular
Disease
8/10 individuals with
diabetes die from CV
events6
Diabetic
Nephropathy Diabetic
Leading cause of
Neuropathy
end-stage renal disease3,4 Leading cause of
non-traumatic lower
extremity amputations7,8

1UK Prospective Diabetes Study Group. Diabetes Res 1990; 13:1–11. 2Fong DS, et al. Diabetes Care 2003; 26 (Suppl. 1):S99–S102. 3The Hypertension in Diabetes Study Group. J
Hypertens 1993; 11:309–317. 4Molitch ME, et al. Diabetes Care 2003; 26 (Suppl. 1):S94–S98. 5Kannel WB, et al. Am Heart J 1990; 120:672–676.
6Gray RP & Yudkin JS. Cardiovascular disease in diabetes mellitus. In Textbook of Diabetes 2nd Edition, 1997. Blackwell Sciences. 7King’s Fund. Counting the cost. The real impact of

non-insulin dependent diabetes. London: British Diabetic Association, 1996. 8Mayfield JA, et al. Diabetes Care 2003; 26 (Suppl. 1):S78–S79.
 Lowering HbA1c reduces the risk of
complications
Deaths related to
21% diabetes

HbA1c
Microvascular
37% complications
1%

Myocardial infarction
14%

Stratton IM, et al. BMJ 2000; 321:405–412.

“The Big Six” of Diabetes
Management

• Glycemic Control
• Hypertension
• Dyslipidemia
• Nephropathy
• Retinopathy
• Foot Care
 Current Treatment Goals for Glycemic Control

ADA ACE IDF

<6.0%
(individual goal)
HbA1c ≤6.5% <6.5%
<7.0%
(general goal)

Preprandial capillary 90–130 mg/dL <110 mg/dL <110 mg/dL

plasma glucose (5.0–7.2 mmol/L) (<6.0 mmol/L) (<6.0 mmol/L)

Peak postprandial <180 mg/dL <140 mg/dL <145 mg/dL

capillary plasma
glucose (<10.0 mmol/L) (<7.7 mmol/L) (<8.0 mmol/L)

ADA=American Diabetes Association; ACE=American College of Endocrinology; HbA1c=hemoglobin A1c; IDF=International Diabetes Federation
Adapted from American Diabetes Association. Diabetes Care. 2006; 29(suppl 1): S4–S42. International Diabetes Federation. Global Guideline for Type 2 Diabetes.
Brussels: International Diabetes Federation; 2005. American Association of Clinical Endocrinologists, American College of Endocrinology. Endocr Pract. 2002;
8(suppl 1): 5–11.
Two thirds of individuals do not
achieve target HbA1c

Saydah SH, et al. JAMA 2004; 291:335–342.

Liebl A, et al. Diabetologia 2002; 45:S23–S28.
Barriers to achieving good
glycemic control
Lack of clarity over definition of
good glycemic control

Inadequate monitoring of glycemia

Complexity of managing hyperglycemia relative to dyslipidemia

and hypertension

Insufficient involvement of specialist

care units
 Diabetes and aging are two major causes for
the ESRD

DM CGN HT TIN Age

Data of 2005, TSN 2006 Hwang SJ 12

 Gene Polymorphism

Polymorphism vs Mutation
Variant alleles occurring in over 1% of population are called
polymorphisms
Variant alleles in less than 1% of population are mutations
Allele frequency varies between populations & families ~
Thus, nutritional requirements & disease susceptibility vary between
populations
Allelic variation fostered by population isolation and cultural, preferential
mating behaviour

www.nutritionmedicine.org
 Gene Polymorphism
Single nucleotide polymorphisms ~
• Single base-pair DNA differences observed
between people
• simplest and most common form of DNA
polymorphism ~
– frequency about of 1/1,000 base pairs
– In any individual, gene polymorphism is estimated
to affect about 10% of the genome
• SNPs may cause disease if they affect expression
of an enzyme-coding gene
– About 1000 monogenic diseases due to SNPs have
been identified

Jimenez-Sanchez G et al. 2001. Nature. 409:853-55

www.nutritionmedicine.org
 Gene Polymorphism and Disease
Maple syrup urine
disease
Thalassemia
MTHFR
Fragile X
deficiency
syndrome
Cystic
Homocystinuria fibrosis
Monogenic Disease
G-6-PD
Phenylketonuria deficiency

Carboxylase
Sideroblastic deficiency
anaemia
Methylmalonyl
CoA deficiency Tay Sachs
disease

www.nutritionmedicine.org
 Gene Polymorphism and Disease
Multigenic disease: e.g. arteriosclerosis
Polymorphisms that regulate expression and activity of genes involved
in blood lipid control are common:
• Occur in 7 – 16% of population
• Apolipoproteins: Apo A-IV, Apo A, Apo B, Apo E
• Lipoprotein lipase
• Cholesterol ester transfer protein
– Affect cholesterol binding and clearance
– Promote hyperlipidaemia, arteriosclerotic disease and dementia
– Alter responses to cholesterol reducing interventions
• Both dietary & pharmacological
• Confound epidemiological & interventional research

Knoblauch H, Bauerfeind A et al. Hum Molec Genet, 2002; 11(12):1477–85.

www.nutritionmedicine.org
 INFLAMMATION
DIABETES
MELLITUS

GENETIC
HIPERTENSION

INFLAMMATION

CARDIOVASCULAR
OBESITY
DISEASE
 TOP PRO-INFLAMMATORY FOODS
FEEDLOT-
DAIRY
RAISED
PRODUCTS
MEAT RED MEAT &
TRANS FAT PROCESSED
MEAT

COMMON ARTIFICIAL
COOKING FOOD
OILS ADDITIVES

REFINED
ALCOHOL
GRAINS

SUGARS INFLAMMATION ?
ENERGY METABOLISM
ENERGY METABOLISM
 METABOLIC DERANGEMENTS
• Diabetes resembles fasting, regarding the
responses of the liver, muscle cells, and
adipose tissues.
• Low serum ratios of insulin to glucagon and a
high levels of fatty acids, the liver produces
glucose, whereas other tissues use fatty acids
& ketones instead of glucose.
 NUTRITION RECOMMENDATION
FOR PERSONS WITH DIABETES

CATEGORY RECOMMENDATION
Weight management Attain & maintain desirable body weight (BMI≤25)
Carbohydrate(% of energy) 55-65%
Polysaccharides Emphasixe whole grains, legumes, vegetables
Monosaccharides and di- Use in moderation
Glycemic index Incorporate into exchanges and teaching material
Fiber, total 25-50 g/d (15-25 g/1000 kcal)
Protein(% of energy) 12-16%
Total fat (% of energy) <30%
SAFA/trans FA(% of energy) <10%
MUFA 12-15%
PUFA <10%
Cholesterol (mg/d) <200 mg/d

From Anderson JW, Randles KM, Kendall CWC et al. J Am Coll Nutr 2004;23:5-17
Nutrition Recommendation for Persons with Diabetes

Nutrient ADA HCF Nutrition Fdnb,c

Carbohydrate, about 50% 50-60%
% of kcal
Proteins, % 10-20% 10-15% (0.8 g/kg)
Fat, total, %  30%d  30%e
Saturated, % <10% <10%
Monounsaturated% 10-20%` 10-15%
Polyunsaturated % <10% <10%
Cholesterol, <300 mg/day <200 mg/day
Fiber, g/day 20-35 g/day about 35 g/day
(15-25 g/1000 kcal
Sodium, mg/day <2400 mg if <1000 mg/1000 kcal
hypertensive
Alcohol  drinks/day Men 2 drinks/day
Women 1 drink/day
Vitamin supplements Not recommended Multivitamin-mineral daily
antioxidant supplements

American Diabetes Association. Nutrition recommendations and principles for people with diabetes mellitus. JADA 1994;94-905
Anderson JW, Geil PB. Nutrition management of diabetes mellitus. In Shils M. Modern Nutrition in Health and Disease, 8th edition.
Philadelphia: Lea & Febiger, 1994;1259-86.
Anderson JW, Professional guide to high fiber fitness plan. Lexington, KY: HCF Nutrition Research Fdn. 1995;10.1-10.22
Individualization recommended. More fat permitted and less carbohydrate acceptable.
Up to 35%of energy from fat can be used for nonobese individuals with acceptable serum triglyceride values if the additional fat comes
from monounsaturated sources and saturated and polyunsaturated fats remain under 10% each.
Glycemic Index (GI) Ranking of Selected Starchy Foods

Class I Class II Class III

(Higher: GI >90) Intermediate: (Lower: GI <70)
GI = 70–90

Most breads Oat bran Pumpernickel bread

Plain crackers Oatmeal Most pasta
Most breakfast Most cookies or Boiled rice
cereals biscuits
Most potatoes polished rice Most dried legumes
Pancake & waffles Whole-wheat bread Nuts
Corn chips Boiled Sweet corn Barley
Most cakes Boiled new potatoes Dry beans & lentils
Yams
Sweet potatoes
A. Glycemic response of nondiabetic individuals to 50 g carbohydrate from new potatoes
or kidney beans. B. Glycemic response of healthy individuals to 50 g of glucose, sucrose, or
fructose
Factors affecting the Glycemic Response to food

Rate of ingestion
Food form
Food components
Fat content
Fiber content
Protein content
Starch characteristic
Methods of cooking and processing
Physiologic effects
Pregastric hydrolysis
Gastric hydrolysis
Gastric emptying rate
Intestinal response
Intestinal hydrolysis and absorption
Pancreatic and gut hormone response
Colonic effects
 High Fiber Intakes Advantages and Disadvantages

Advantages
Slow nutrition digestion and absorption
Decrease postprandial plasma glucose
Increase tissue insulin sensitivity
Stimulate glucose use
Attenuate hepatic glucose output
Decrease counterregulatory hormone release (e.g.,glucagon)
Lower serum cholesterol
Lower fasting and postprandial serum triglycerides
May attenuate hepatic cholesterol synthesis
May increase satiety between meals
Disadvantages
Increase intestinal gas
Temporarily may cause abdominal discomfort or gastrointestinal
distress
May alter pharmacokinetics of certain drugs
 However, The major influence
on genomic disease is probably
the gross discrepancy
between our human ancestral genome
and the modern consumer-age diet

www.nutritionmedicine.org
Following the last Ice-Age 12,000 years ago, the birth of agriculture 10,000
years ago  Settled lifestyle and increased population density
~ increased demand for intensive farming & animal husbandry – which
occurred about 8,000 years ago
~ greater starch-yielding grain crops
~ increased gluten content in grains
~ altered fat content in animals from supplemental feeding
~ Industrial revolution altered food supply even further
~ farming monoculture developed
~ increased dependence on grains
~ refined sugars became more accessible
~ increased fat and trans-fat intake
~ increased omega-6/omega-3 EFA ratio
Bradshaw Foundation. www.bradshawfoundation.com/stephenoppenheimer
www.nutritionmedicine.org
 Paleolithic diet: Modern Diet
Protein ~ 30-40% 10-20%
Carbohydrates ~ 35% 60-70%
sugars ~ 2-3% 15%
Fats ~ 30-35% 30-35%
Saturated fats ~ 7.5% 15-30%
Trans-fat < 1% 5-10% of fats
Omega-6/omega-3 ~ 2:1 10-20:1
Potassium : Sodium 5:1 1 :2

www.nutritionmedicine.org
 DASH Reduces Homocysteine Levels

• Effect a result of diet high in vitamin B-rich

milk and milk products, fruits and vegetables
• Lowering homocysteine with DASH may
reduce CVD risk an additional 7%-9%

Appel, et al. Circulation, 102:852, 2000

7/29/2011 PBRC 2011 32

 DASH Diet Pattern
based on a 2,000 calorie diet

Food Group Servings*

Grains 6-8
Vegetables 4-5
Fruits 4-5
Low-fat or fat free dairy 2-3
Meats, poultry, fish less than 6
Nuts, seeds, dry beans and peas 4-5/week
Fats and oils 2-3
Sweets 5/ week
Sodium 2300 mg

* Per day unless indicated

7/29/2011 PBRC 2011 33

 Dash Diet

• Slowly increase intake of

fruits and vegetables to 8
or more per day
• Nuts, seeds and dried
beans 4-5 times per
week
• Good source of
potassium and
magnesium. Help
reducing blood pressure
7/29/2011 PBRC 2011 34
 DASH Diet continues...

• More whole grain

cereals and breads
• 6 ounces or less of
meat, fish or poultry
per day
• Small amounts of
liquid or soft
margarine or oil

7/29/2011 PBRC 2011 35

 Eat Less Sodium

• DASH is more effective

if also reduce sodium
• Less than 2400
milligrams per day
• Reduce slowly in 2-3
weeks so that taste
buds will get use to less
salt

7/29/2011 PBRC 2011 36

 Ways to Cut Sodium
We get most of our salt
from convenience foods.
• Use unsalted canned or
frozen vegetables. If use
regular, rinse canned
foods to reduce sodium.
• Choose convenience
foods low in salt when
available.
• Use fewer convenience
foods
• Compare labels

7/29/2011 Image:PBRC
http://www.nlm.nih.gov
2011 37
 Ways to Cut Sodium

• Most restaurant foods

are very high in
sodium
• Eat out less often
• Make more foods
from scratch.

7/29/2011 PBRC 2011 38

 • Look for the
amount of sodium
in foods by finding
it on the Nutrition
Facts Label.
• Choose foods that
have lower amount
of sodium based on
the label.

7/29/2011 PBRC 2011 39

 USE SEA SALT!
• GARAM LAUT YANG ORISINIL
• GARAM GANDU KASAR, DAPAT DIPEROLEH DI
PASAR
• KANDUNGAN GIZI: MAGNESIUM, KALIUM,
NATRIUM, KLORIDA, ZINC,
 HCG Diet
• Human Chorionic Gonadotropin is hormone produced only
during pregnancy.
• HCG first used in 1930 by Dr. A.T.W. Simeons to treat obesity.
• Claims: decrease appetite, mobilize fat burning cells through
action in the hypothalamas, while sparing muscle cells.
• Research: No quality studies have shown that HCG itself helps
weight loss. Rather, the following of a very low calorie diet is
likely the reason for weight loss regardless of the use of HCG
(Mayo Clinic, Rowan, Dale).
 HCG Diet
• 500 calorie diet along with daily injections of HCG
• Homeopathic HCG drops are cheaper and safer.
• HCG diet : carbohydrate from fruits, protein from
fish / chicken breast / egg / beans / nuts, fat from
fish, avocado, olive oil, grapeseed oil, vegetables
and fruits for fiber, vitamin, and mineral. No deep
fried food
• Eat reasonable amount of fruits and vegetables,
good source of potassium and magnesium
 RAW FOOD DIET

• KONSUMSI MAKANAN YANG TIDAK DIMASAK

• JIKA DIMASAK, SUHU TIDAK LEBIH DARI 80
DERAJAT CELCIUS
• CARA MASAK: TUMIS CEPAT, KUKUS
• JUMLAH SAYURAN DAN BUAH 1 KG PER HARI
ECO Recommendation

Meat, fish,
beans, eggs,
cheese
Vegetables,
Salad
R-Lipoic acid
R-dihydro Lipoic acid (DHLA)
 BETA CAROTENE
• Influence in growth and cell differentiation
• Neutralize free radicals
• RDA vitamin A: 1000 IU – 3000 IU
• Antioxidant dosage: 8000 IU – 10.000 IU
• Source: cod liver oil, pumpkin, carrot, spinach
 VITAMIN C: CALCIUM ASCORBATE
• Boost immune system
• Neutralize degenerative effect of free radicals
• Collagen synthesis
• Formation of bone and teeth
• 4th generation of Vitamin C (1. ascorbic acid , 2.
vit C+Na, 3. Ester-C Ascorbic)
• RDA: 60 mg – 90 mg
• Antioxidant dosage: 200 mg – 3000 mg
• Source: orange, strawberry, chili, broccoli
 Vitamin D (the sunshine vitamin)
 Functions:  Dosage: 1000-2000 mg/d
Promotes absorption or 1000-2000 IU
of calcium and  Sources:
phosphorus Sunlight (10 – 15 mins
Helps deposit those 2x a week)
in bones/teeth Salmon with bones
Regulates cell growth Orange juice (fortified)
Plays role in
immunity
VITAMIN E: ALPHA-TOCOPHEROL AND
GAMMA-TOCOPHEROL
• Maintain cell structure and function
• Neutralize Reactive Nitrogen Oxide Species
(peroxynitrite dan nitrogen dioxide)
• Protect white blood cell and involve in imune
system
• RDA 6 IU – 28,5 IU
• Antioxidant dosage: 200 IU – 600 IU
• Source: olive oil, canola oil, sunflower oil,
almond, hazelnut, peanut
 GLUTATHIONE PRECURSOR
• Support immune system
• Regenerates vitamin C and vitamin E
• Precursor: NAC (N-Acetyl-L Cystein) depends
on: selenium, vitamin C & E, and R-dihydro
Lipoic Acid (DHLA)
 ALPHA-LIPOIC ACID (ALA) & R-
DIHYDRO LIPOIC ACID (DHLA)
• Strong antioxidant, soluble both in water and
fat.
• Regenerates vitamin C, vitamin E, glutathione,
and CoQ10
• Reduce glycation effect (cross link protein and
glycogen)
• Antioxidant dosage: 200 mg – 400 mg
 Co ENZYME Q10 (CoQ10)
• Play a key role in energy production in
mitochondria
• Optimize oxygen supplies to the whole body
• Protects DNA and cell membrane from lipid
peroxyl.
• Supplement dosage : 30 mg – 100 mg
• Antioxidant dosage : 100 mg – 300 mg
 Acetyl L-Carnitine (ALC)
• Delay the onset of age-related cognitive and
improves overall cognitive function in elderly
• Improve memory, mood, and response to stress
• Reduce lipid peroxidation, reduce necrotic damage
and infarct size, preserve myocardial levels of ATP
• Cofactor in mitochondrial energy production by
transporting activated fatty acids in cardiac and
skeletal muscle
• Increase maximal aerobic power
• Antioxidant dosage : up to 1500 mg daily
 DOCOSAHEXAENOIC ACID (DHA)
EICOSAPENTAENOIC ACID (EPA)
OMEGA-3
• Anti inflammation effect
• Fat burner
• Prevent platelet aggregation
• Help to build brain cell and nerve
• Supplement dosage: 500 mg – 2000 mg DHA +
EPA
• Herring, salmon, sardines, tuna
 OMEGA-9 FATTY ACID
• Anti-inflammatory effect
• Anti-allergic effect
• Food source: olive oil, avocado, macadamia
nuts
 SESAME LIGNAN
• Works with gamma tocopherol, fish oil
(increase vit E & DHA, prevent lipid
peroxidation) dan Conjugated Linoleic Acid
(CLA)
• Improve fat profiles
• Fat burner
• Strong antioxidant
 BIOFLAVONOIDS
• Pycnogenol (pine bark – oligomeric
proathocyanidin complexes)
• Curcumin (strong phase II conjugation activity)
• Green tea (Epigallocatechin gallate – EGCG)
• Grape seed extract (proanthocyanidin; anti-
inflammatory effect)
• Anti inflammation effect
• Anti oxidants effect : 500 – 2000 mg daily
 SYNBIOTIC
• Prebiotic + Probiotic
• Anti-microbial qualities, anti-allergenic qualities,
anti-diarrheal aspects, reduces serum fats and
blood sugars
• The best synbiotic combinations currently
available include bifidobacteria and fructo-
oligosaccharides (FOS), Lactobacillus GG and
inulins, and bifidobacteria and lactobacilli with
FOS or inulins
• Food source: yoghurt and kefir
 SUPLEMEN NATURAL LAINNYA
• RHODIOLA
• GLUTAMIN
• OPHIOCEPHALUS STRIATUS
• CARPARIS SPINOSA
• ASHWAGANDA
• GINGER
• CURCUMIN
• NIGELLA SATIVA