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Obesity: nutrients modulators of
neuropeptides and
neurotransmmitters
NUTRIGENOMIC MODULATION OF
OBESITY AS A RISK FACTOR ...
Today, one in three of the world’s
adults is overweight and one in 10
is obese.
By 2015, WHO estimates the
number of chubb...
Causes of obesity:
 Food: level of carbohydrates
 Stress; cortisol and catecholamine
glicogenolisis
fatty acids
adipocit...
Pulmonary disease
abnormal function
obstructive sleep apnea
hypoventilation syndrome
Nonalcoholic fatty liver
disease
stea...
Complications of Obesity
 Cardiovascular Diseases
 Rheumatoid Diseases
 Diabetes and complications
 Hypertension
 Str...
Table 2. Increased Risk of Obesity Related Diseases
with Higher BMI
Disease BMI of
25 or less
BMI between
25 and 30
BMI be...
How to measure levels of
obesity:
 É o excesso de gordura corporal em relação à massa magra.
 Pode ser classificada pelo...
Intra-abdominal Fat
Abdominal Waist=> >94cm in men = risk
>102cm in men = severe
>80cm in women = risk
>88cm in women = se...
Vital Statistic:Vital Statistic: Waist CircumferenceWaist Circumference
Abdominal circunference
HIgher risk
SINETROL
 Extrato de frutas cítricas (laranja vermelha, toranja e
citrus)
 Constituintes químicos: biofenóis, guaraná e
...
COLLEFORIN
 Extrato padronizado que contém no mínimo 10% de
forskolin,
 Aumenta a adenilato ciclase – Lipólise
 Estimul...
COLLEFORIN
COLLEFORIN
During two weeks,
I diet,
I exercised,
I took my pills and
I lost fourteen dayss.
STRESS
 OBESITY FACTOR
OBESITY
IME W
H2
BETTER ABDOMINAL CIRCUNFERENCE
84CM 102 CM
WOMEN MEN
OMEGA 3+GLA A R
BORRAGE OIL VISCERAL FAT BOOY SHAPE
...
 VISCERAL FAT
 CYTOKINES INHIBITED CURCUMIN
 BOSWELLIA
 ANTI OXIDANTES
Stress oxidativo
 Medir mda
CHRONIC
STREES CORTISOL GLICOGENOLYSIS RISE BLOOD
SUGAR (IF NOT CONSUME BY CELLS –
INSULIN RESISTANCE)
GLICEROL 3 – PHOSPH...
CHRONIC STRESS DECREASE AFTENOON CORTISOL
TO EXAUSTION (CIRCADIAN RYTHM)
GLICOGENOLYSIS
HUNGER BY HHA
ACHT LOW CORTISOL RE...
CORTISOL SEROTONIN
TRIPTOPHANE DHEA TESTOSTERONE
DISBIOSIS
5HTP SEROTONINE
Flora bacteriana intestinal
 Disbiose
 Ph da saliva
 Transito intestinal
 hipocloridria
CORTISOL INTRACELULAR LEVEIS OF ZN
ZN CORTICAL REGION (SUPRARRENAL)
ZN 5 BETA REDUCTASE (LIVER)
BOTH
CREATE AND DESTROY CO...
CORTISOL BIOAVABILITY OF ZN
TESTOSTERONE
LOW ACTIVITY OF 5 ALFA REDUCTASE
5DHT(DECREASE) AROMATASE(INCREASE)
STRESS
ZN DEPENDENT
SE
T4
2-5 T3 EUTHYROID SICK SYNDROME
DIODINASE
DECREASE
stress
 Medir stress adrenal
DIET: PROTEIN
CARBOHIDRATES
FAT
MICRO AND MACRONUTRIENT FOOD MODULATORS
BEST?
PHYSICAL ACTIVITY
PLEASURE (STRESS-OBESITY)
EXCESS
NUTRITIONAL THERAPY FOR PHYSICAL ENDURANCE
CREATINE NADH
CARNITINE COQ10
D – RIBOSE WHEY PROTEIN
COQ10 GLUTAMINE
BCAA
Dieta ken
Only protein diet has been used successfully to
prevent loss of lean body mass first in post-
surgical
and then in obese p...
The 24-hour infusion was controlled with
a small portable
pump. Before and after each 10-day
cycle body composition was ch...
Conclusion:
KetogenicEnteral Nutrition treatment of
over 19,000 patients induced a rapid
10% weight loss, 57% ofwhich was ...
Table 2 (g%) Composition of the
nutrition powder
(K1000W)
Proteins 90.0
Carbohydrates 1.80
Fats 0.80
Calcium 0.40
Potassiu...
However, the KEN diet differs from the
PSMF diet in several key points;[17]
● Protein intake is supplemented
continuously ...
● Daily protein intake is reduced to 50
g for women and 65 g for men (an
average of 0.86 g/kg of ideal body
weight) consid...
● Carbohydrate intake is completely
eliminated; during each treatment
cycle patients are permitted to drink
only water or ...
Treatment complications:
Asthenia 24%
Mild sense of hunger 12%
Constipation (need to increase
Macrogol) 5%
Problems with t...
In principle, only 3 categories of patients cannot be subjected to
KEN:
a) Patients who cannot take a normal amount of pro...
Introduction of the NasogastricTubeIt is necessary to slowly infuse the
solutions of protein during the 10 days cycle. The...
ObesityandWeightLoss
The Nine Pillars of Successful Weight Loss that should not be
overlooked if healthy weight management...
Insulin Resistance and/or LeptinResistance
In addition to being a result of obesity, elevated levels of the hormones lepti...
Sex Hormone and Thyroid Hormone Insufficiencies/ Imbalances
Levels of sex hormones (such as testosterone and dehydroepiand...
Obesity and low testosterone have a complex
relationship; low testosterone can be considered
both a cause andconsequence o...
Thus, in older men with excessive
abdominal fat, the ratios of
testosterone to estrogen are lower than
in younger men. Ele...
The thyroid is a central regulator of
metabolism; it integrates signals from
the brain and secretes thyroid
hormone (thyro...
HCG
 First discovered by Ascheim and
Zondek as back as 1927 in the
urine from pregnant women
(2,67), thousands of article...
HCG
 The three pituitary hormones
 LH (Luteinising Hormone), FSH
(Follicle Stimulating Hormone)
and
 TSH (Thyroid Stimu...
The first report on hCG and obesity was
published back as 1954 in The Lancet,
by a British physician, Dr. A.T.W.
Simeons (...
Simeons ATW.:
The action of chorionic gonadotropin in the obese. Lancet
II: 946-947. 1954
HCG
 This is a glycoprotein hormone that can melt
abnormal fat banks in the body and accelerate
metabolism. Obese people,...
 Hcg treatment for obesity really
works because in this diet plan
an overweight individual have to
maintain a VLCD protoc...
The Three Stages of HCG Protocol
are:
 Load days: In this period, the
patient is allowed to consume high
fat containing f...
The Three Stages of HCG Protocol
are:
 Maintenance (M1 & M2): During the last
period of protocol, the body’s metabolic ra...
TEST
STANDARD REFERENCE
RANGE
OPTIMAL LEVEL
Thyroid-stimulating
hormone (TSH)
0.4 – 5.0 µIU/mL 1.0 – 2.0 µIU/mL
Free thyro...
Total testosterone
Men
348 – 1197 ng/dL
700 – 900 ng/dL
Women
8 – 48 ng/dL
35 – 45 ng/dL
Free testosterone
Men
Age 20 – 29...
Insulin 2.6 – 24.9 µIU/mL
<5 µIU/mL
Glucose
(fasting)
65 – 99 mg/dL
70 – 85 mg/dL
Blood Pressure
(optimal)
≤120 / 80 mmHg
...
Overeating and Dining Out
Increases in daily average food consumption significantly contribute to weight gain in the Unite...
In an effort to avoid the caloric excess to which so many restaurant-goers succumb,
suppression of hunger signals is likel...
Obesity: nutrients modulators of
neuropeptides and
neurotransmmitters
What Are
Neurotransmitters?
Neurotransmitters serve as
messengers, transmitting
information from one nerve
cell to another...
naltrexone
 As of May 2004:In preparing a proposed
clinical trial protocol for the use of LDN in the
treatment of multipl...
naltrexone
 As of March 2002:Clinically the results
are strongly suggestive of efficacy.
Ninety-eight to 99% of people tr...
Inhibitory
•Seroton
in
•Gaba
•Taurine
•Glycine
Excitatory
•Epinephrine
•Norepinephrine
•Dopamine
•Glutamate
•Phynylethylamine (PEA)
Excite & Inhibit
•Serotonin can be both
excitatory and
inhibitory
The Most Common Deficiency
SEROTONIN
Serotonin Deficiency
•Carbohydrate cravings
•Migraine
•Premenstrual
syndrome
•Depression
•Insomnia
•Obsessive-compulsive
•...
Serotonin Precursors
•Tryptophan
•5-htp-5 hydroxitryptophan
•Grifonia
•saffrin
Serotonin Herbs
•St. John’s wort
•Rhodiola
LEVELS OF SEROTONINE
GRIFFONIA
5 HTTP TRYPTOPHANE
DRUGS: SISR (SELETIVE INHIBITORS OF SEROTONINE REUPTAKE)
Dopamine Deficiency
•Sugar/caffeine
cravings
•Fatigue, Lightheadedness
•Pallor
•Diarrhea
•Decreased libido
•Routine-task d...
 LOW DOPAMINE
PHENYLALANINA
 TYROSINE MUCUNA EuPHORIA
 CAFFEIN BLOCK DOPAMINE
ADENOSINE TIRED
Dopamine Precursors
•Tyrosine
•CAFEINA
•D,L – phenylalanine
•Mucuna
•GING SENG
Figure 1. Dopaminergic pathways.
(a)Dopaminergic pathways. PFC, prefrontal cortex; CG,
cingulate gyrus; OFC, orbitofrontal...
Epinephrine Excess
•Anxiety
•Hyperactivity
•Stress
•Carbo
eating
Norepinephrine Deficiency
•Fibromyalgia
•Mood disorders
• salt craving
•PMS
•Very strenuous exercise
Epi-norepi precursors
 Phenylalanine
 Mucuna
 tyrosine
TYROSINE
DOPAMINE
TRYPTOPHAN GLUTAMINE
GABA
2. Each individuals health
benefits from having the right
molecules in the rig...
Gaba functions
•Modulates orther
neurotransmitters
•Calms the brain rhythms
•Induces alpha brain waves
Gaba Deficiency Symptoms
•Flushing
•Tachycardia, Palpitations
•Trembling, Twitchy
•Cold, Clammy hands
•Carbohydrate
cravin...
Gaba precursors
 Theanine
 Kava kava
 Taurine
 Glutamine
 Benzodiazepines
 Valeriane
 passiflorine
THEANINE
GREEN TEA
“Theanine, when reaching the brain, has
been shown in rats to increase both
serotonin and dopamine prod...
Neutopeptides and Obesity
Hungry Hypothalamic
Satiety Nucleus
Leptina => with gaining weight
Produced by Direct Relationship
Gene OB
With loosing weight
Fatty Cells
slow relationship=g...
(Biochim. Biophys. Acta
2005 May 30; 1740 (2) 293-
304
Leptine => Inhibits
NPY(neuropeptide Y)=> Levels
Leptine Empty Stom...
Resistina=> weight => insulin resistance
Adiponectina => weight => insulin sensibility
Modulation: Food glicemic index
Chr...
NPY=> Neuropeptide Y
36 amino acids peptide
anabolic effectors (hungry)
inhibits thermo genesis
During fasting
After eating
NPY Modulators
 Slow absorbing foods
 5HTP
 Protein Supplement
 Drugs that increase shtp recaptation
•Protein
•Fatty A...
Peptide YY (PYY) is secreted from the endocrine L cells of
the small and large bowel, and release into the circulation
aft...
MODULATION OF PPY
 FOOD PROTEIN AND COMPLEX CARBOHYDRATES
 INCREASING CCK
 ADMINISTERING AMINOACIDS OR PEPTIDES
“Marijuana and its major
psychotropic component, 9-
tetrahydrocannabinol, stimulate
appetite and increase body
weight in w...
Cannabinoides (Modulators)
 Rimonabant
 Pholia Magra (Boraquinaceas family)
(Pau-de-vira-tripa means high
and skinny per...
CCK=> Cholecystokinin=> released by the GI system
close pylori sphincter
keeps longer time food in stomach
inhibit NPY
Is ...
CCK Modulators
 Food rich in protein
 Amino acids like phenylalanine and tyrosine
 Slendesta (proteinase II inhibitor=>...
Ghreline=> secreted by all cell of the gastric mucose during fasting
immediately after eating
Neural Control
Hunger, diges...
Modulators of ghrelin
 Amino acids
 Slow release food
 Bariatric surgery
PPAR => peroxisomes
Alfa=Liver heart muscle kidney
Gamma => adiposity tissue and macrophages
Delta unknown
Reduces heavy f...
Modulators
 Rosiglitazone
 Fibrates
 PUFA
 CLA
 curcumin
Incretines:
GPI (Glicose Insulinotropic polipeptide)
Releases insuline induced by glicose.
Inhibited by
DPP4
 Level of incretin rises 60% with feeding in normal patients
 Level rises only 6% in diabetics
Modulators
 DPP4 Inhibitors: Vildagliptina
Sildagliptina
 GPI Agonists: exenatide
 Nutrients: Irvingia Gambonienses
Cart=> Cocaine and amphetamine regulated transcript
Located at
the arcuate
nucleus
Increases hunger
ARGININE:NO
CART
 Intra-nuclear injection of CART has
produced effects different from
intracerebroventricular injections.
CART inject...
Cart
 Arginine
 Anphetamines
 Anphetamines like
 5htp
TEST
STANDARD REFERENCE
RANGE
OPTIMAL LEVEL
Thyroid-stimulating
hormone (TSH)
0.4 – 5.0 µIU/mL 1.0 – 2.0 µIU/mL
Free thyro...
Total testosterone
Men
348 – 1197 ng/dL
700 – 900 ng/dL
Women
8 – 48 ng/dL
35 – 45 ng/dL
Free testosterone
Men
Age 20 – 29...
Insulin 2.6 – 24.9 µIU/mL
<5 µIU/mL
Glucose
(fasting)
65 – 99 mg/dL
70 – 85 mg/dL
Blood Pressure
(optimal)
≤120 / 80 mmHg
...
Cancer
Obesity is a risk factor for several types
of cancer.
White adipose tissue (ie, “bad fat”) can
secrete a variety of...
Postmenopausal breast cancer risk increases with obesity, possibly through
effects on systemic inflammation, or increases ...
Obesity may increase thyroid cancer
risk; the rise in thyroid cancer incidence
parallels that of obesity, although
studies...
Eat for a Long and Healthy Life
Caloric restriction. Caloric restriction is the dramatic reduction of dietary calories to ...
DIET: PROTEIN
CARBOHIDRATES
FAT
MICRO AND MACRONUTRIENT FOOD MODULATORS
BEST?
Dieta ken
Only protein diet has been used successfully to
prevent loss of lean body mass first in post-
surgical
and then in obese p...
The 24-hour infusion was controlled with
a small portable
pump. Before and after each 10-day
cycle body composition was ch...
Conclusion:
KetogenicEnteral Nutrition treatment of
over 19,000 patients induced a rapid
10% weight loss, 57% ofwhich was ...
Table 2 (g%) Composition of the
nutrition powder
(K1000W)
Proteins 90.0
Carbohydrates 1.80
Fats 0.80
Calcium 0.40
Potassiu...
However, the KEN diet differs from the
PSMF diet in several key points;[17]
● Protein intake is supplemented
continuously ...
● Daily protein intake is reduced to 50
g for women and 65 g for men (an
average of 0.86 g/kg of ideal body
weight) consid...
● Carbohydrate intake is completely
eliminated; during each treatment
cycle patients are permitted to drink
only water or ...
Treatment complications:
Asthenia 24%
Mild sense of hunger 12%
Constipation (need to increase
Macrogol) 5%
Problems with t...
In principle, only 3 categories of patients cannot be subjected to
KEN:
a) Patients who cannot take a normal amount of pro...
Introduction of the NasogastricTubeIt is necessary to slowly infuse the
solutions of protein during the 10 days cycle. The...
Intermittent fasting
 Intermittent fasting (IF) describes diets that cycle between a
period of fasting and non-fasting. I...
Variations
One form of intermittent fasting, alternate day fasting (ADF), involves a 24-hour
fast followed by a 24-hour no...
Increase Physical Activity
Increased physical activity promotes weight loss by addressing both sides of the
energy balance...
PHYSICAL ACTIVITY
PLEASURE (STRESS-OBESITY)
EXCESS
NUTRITIONAL THERAPY FOR PHYSICAL ENDURANCE
CREATINE NADH
CARNITINE COQ10
D – RIBOSE WHEY PROTEIN
COQ10 GLUTAMINE
BCAA
Restore Resting Energy Expenditure
Black coffee consumption. Black coffee consumption has been
associated with reductions ...
Green tea polyphenols. Green tea has
exhibited anti-inflammatory activity in dozens of
laboratory and animal studies (Sing...
Fucoxanthin. Fucoxanthin is a carotenoid from brown
seaweed that has been shown to reduce white fat levels in
animal model...
Fish oil. Fish oil, a rich source of the omega-3 fatty acids eicosapentaenoic
acid (EPA) and docosahexaenoic acid (DHA), c...
Capsaicin/ Cayenne. Capsaicin is a major “spicy”
constituent of chili peppers (eg, cayenne). Regular intake
of chili peppe...
Restore Healthy Adipocyte (Fat Cell) Signaling
Irvingiagabonensis. Irvingiagabonensis is a mango-like West African
fruit; ...
Sphaeranthusindicus and Mangosteen
(Garciniamangostana). Mangosteen has long
been used as a diabetic treatment in Southeas...
Control Rate of Carbohydrate
Absorption
Green coffee extract. Green coffee
extract, an antioxidant-rich mixture
from unroa...
A study follow-up showed that, contrasting with food-restriction diets, a
surprising 87.5% of the test subjects were able ...
L-arabinose. Sucrose (common sugar) is composed of 2 simple sugar molecules, glucose and
fructose. It is poorly absorbed i...
Glucomannan. Glucomannan is a soluble fiber derived
from Amorphophalluskonjac. It is thought to prolong
gastric emptying t...
sacietogenicos
 Colageno
 In cell
 Aminoacidos
 Whey protein
Restore Youthful Hormone Balance
Hormone replacement therapy, using natural compounds like dehydroepiandrosterone
(DHEA) a...
Restore Insulin Sensitivity
Restoring the function of insulin at the cellular level is paramount to
combatting diseases re...
Inibidores de liberacao de
insulina
 D-ribose
 Opuntia500 mgs
 Fasciolamina
 metformina
Inhibit the Lipase Enzyme
The lipase enzyme is responsible for facilitating the absorption of dietary fats. Taking steps t...
Eat to Live a Long and Healthy Life
Life Extension encourages anyone striving to lose weight to consider
adopting a calori...
RestoreHealthyAdipocyte (Fat Cell) Signaling
• Irvingiagabonensis: 150 mg twicedaily
• SphaeranthusindicusandMangosteen (G...
RestoreYouthfulHormoneBalance
• Dehydroepiandrosterone (DHEA): 15 – 25 mg daily for women; 25 – 75 mg daily for men
(depen...
Propolmannan
Take at least two hours apart from medications. Because this product may
lower blood glucose, consult your he...
Dopamine-Urine (g/gCr)
Serotonin- -Urine (g/gCr)
GABA -Urine (mol/gCr)
Creatinine -Urine (mgdL)
195,3
69,8
21,4
38,6
12...
Lentra ™
Lentra ™ é uma fórmula ansiolítica natural, visando receptores GABA-
A. Suporta caminhos que ativam a neurotransm...
Lentra ™
Prolent ™
 Prolent ™ é usado em, restauração, e as fases de
manutenção inicial para reconstruir ou manter o
sistema inibi...
Prolent ™
Tranquilent ™
 Única, mastigável, com sabor de
framboesa fórmula fornecendo
suporte para o sistema inibitório -
tanto ser...
Tranquilent ™
FÓRMULAS EXCITATÓRIAS
 Os produtos de apoio excitatórios são projetados
para aumentar a produção de catecolaminas,
dopami...
Contegra ™
 Contegra ™ é uma fórmula de apoio
de amplo espectro para o "fio e
cansado", apoiando a produção
inibitório e ...
Contegra ™
Procite-D™
 Procite-D ™ é uma fórmula de apoio
visando especificamente
catecolaminas dopamina apoiando
simultaneamente no...
Procite-D™
FÓRMULAS DE APOIO
Junto com as fórmulas
inibitórios e excitatórios
de apoio, a linha de
produtos TNT ™ também
inclui fórm...
SomniTR ™
 SomniTR ™ é uma fórmula atrasou-
lançado, destinado a liberação de 1 mg
de melatonina inicialmente e 1 mg três...
SomniTR ™
MethylMax ™
 A fórmula de metilação de espectro total para o
apoio de todos as principais vias de metilação.
MethylMax ™
Adaptacin ™
 A fórmula para os pacientes com
necessidade de apoio adrenal. Este
produto utiliza a mais alta qualidade, a
...
Adaptacin ™
Plenus ™
 Plenus ™ é um produto avançado saciedade
para enfrentar excessos e perda de peso. Ela
representa a vanguarda da...
Plenus ™
WHAT IS THE GOAL
• REDUCE OXIDATIVE STRESS
• REDUCE VISCERAL FAT
• REDUCE LDL OXDIATION
• REDUCE INSULIN RESITANCE
• INCRE...
WHAT IS THE GOAL
 REDUCE BETA AMYLOID TISSUE IN THE BRAIN
 REDUCE STRESS AND ADRENAL FATIGUE
 INCREASE SACIETY NEUROPET...
Obesity: nutrients modulators of neuropeptides and neurotransmmitters
Obesity: nutrients modulators of neuropeptides and neurotransmmitters
Obesity: nutrients modulators of neuropeptides and neurotransmmitters
Obesity: nutrients modulators of neuropeptides and neurotransmmitters
Obesity: nutrients modulators of neuropeptides and neurotransmmitters
Obesity: nutrients modulators of neuropeptides and neurotransmmitters
Obesity: nutrients modulators of neuropeptides and neurotransmmitters
Obesity: nutrients modulators of neuropeptides and neurotransmmitters
Obesity: nutrients modulators of neuropeptides and neurotransmmitters
Obesity: nutrients modulators of neuropeptides and neurotransmmitters
Obesity: nutrients modulators of neuropeptides and neurotransmmitters
Obesity: nutrients modulators of neuropeptides and neurotransmmitters
Obesity: nutrients modulators of neuropeptides and neurotransmmitters
Obesity: nutrients modulators of neuropeptides and neurotransmmitters
Obesity: nutrients modulators of neuropeptides and neurotransmmitters
Obesity: nutrients modulators of neuropeptides and neurotransmmitters
Obesity: nutrients modulators of neuropeptides and neurotransmmitters
Obesity: nutrients modulators of neuropeptides and neurotransmmitters
Obesity: nutrients modulators of neuropeptides and neurotransmmitters
Obesity: nutrients modulators of neuropeptides and neurotransmmitters
Obesity: nutrients modulators of neuropeptides and neurotransmmitters
Obesity: nutrients modulators of neuropeptides and neurotransmmitters
Obesity: nutrients modulators of neuropeptides and neurotransmmitters
Obesity: nutrients modulators of neuropeptides and neurotransmmitters
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Obesity: nutrients modulators of neuropeptides and neurotransmmitters

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Expositor: Efrain Olszewer
Obesity: nutrients modulators of neuropeptides and neurotransmmitters.
Arequipa 2015

Published in: Healthcare
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Obesity: nutrients modulators of neuropeptides and neurotransmmitters

  1. 1. Obesity: nutrients modulators of neuropeptides and neurotransmmitters NUTRIGENOMIC MODULATION OF OBESITY AS A RISK FACTOR OF SENILITY DR. EFRAIN OLSZEWER CMP-FAPES-BRAZIL-2014
  2. 2. Today, one in three of the world’s adults is overweight and one in 10 is obese. By 2015, WHO estimates the number of chubby adults will balloon to 2.3 billion — equal to the combined populations of China, Europe and the U.S.
  3. 3. Causes of obesity:  Food: level of carbohydrates  Stress; cortisol and catecholamine glicogenolisis fatty acids adipocites  Hypothyroidism  Sedentarism  Others (Drugs)
  4. 4. Pulmonary disease abnormal function obstructive sleep apnea hypoventilation syndrome Nonalcoholic fatty liver disease steatosis steatohepatitis cirrhosis Coronary heart disease Diabetes Dyslipidemia Hypertension Gynecologic abnormalities abnormal menses infertility polycystic ovarian syndrome Osteoarthritis Skin Gall bladder disease Cancer breast, uterus, cervix colon, esophagus, pancreas kidney, prostate Phlebitis venous stasis Gout Medical Complications of Obesity Idiopathic intracranial hypertension Stroke Cataracts Severe pancreatitis
  5. 5. Complications of Obesity  Cardiovascular Diseases  Rheumatoid Diseases  Diabetes and complications  Hypertension  Stroke, ITA  Others
  6. 6. Table 2. Increased Risk of Obesity Related Diseases with Higher BMI Disease BMI of 25 or less BMI between 25 and 30 BMI between 30 and 35 BMI of 35 or more Arthritis 1.00 1.56 1.87 2.39 Heart Disease 1.00 1.39 1.86 1.67 Diabetes (Type 2) 1.00 2.42 3.35 6.16 Gallstones 1.00 1.97 3.30 5.48 Hypertension 1.00 1.92 2.82 3.77 Stroke 1.00 1.53 1.59 1.75 Source:CentersforDiseaseControl.ThirdNationalHealthand NutritionExaminationSurvey.AnalysisbyTheLewinGroup,1999. http://www.obesity.org/treatment/cost.shtml
  7. 7. How to measure levels of obesity:  É o excesso de gordura corporal em relação à massa magra.  Pode ser classificada pelo índice de massa corpórea: < 18,5 18,5 a 24,9 25 a 29,9 > 40 Magro Normal Sobrepeso Obeso Mórbido 30 a 39,9 Obeso Kg/m2 IMC= Peso/Altura2
  8. 8. Intra-abdominal Fat Abdominal Waist=> >94cm in men = risk >102cm in men = severe >80cm in women = risk >88cm in women = severe citokines IL-I IL-VI TNF Inflammation
  9. 9. Vital Statistic:Vital Statistic: Waist CircumferenceWaist Circumference Abdominal circunference HIgher risk
  10. 10. SINETROL  Extrato de frutas cítricas (laranja vermelha, toranja e citrus)  Constituintes químicos: biofenóis, guaraná e cafeína.  Lipolítico: ↑ AMPc pela inibição Catecol-metil transferase e fosfodiesterase.  Posologia:350mg-1g
  11. 11. COLLEFORIN  Extrato padronizado que contém no mínimo 10% de forskolin,  Aumenta a adenilato ciclase – Lipólise  Estimula a termogênese - AMPc DOSAGEM: 250-500mg/dia. Obesity Research 13:1335-1343 (2005)
  12. 12. COLLEFORIN
  13. 13. COLLEFORIN
  14. 14. During two weeks, I diet, I exercised, I took my pills and I lost fourteen dayss.
  15. 15. STRESS  OBESITY FACTOR
  16. 16. OBESITY IME W H2 BETTER ABDOMINAL CIRCUNFERENCE 84CM 102 CM WOMEN MEN OMEGA 3+GLA A R BORRAGE OIL VISCERAL FAT BOOY SHAPE HOMEM MULHER PGE II INFLAMMATION RELEASE CYTOKINES MDA THROMBOYANE OMEGA 6 LINOLEIC ACID ARACHIDONIC ACID THROMBOXANE PGE II MDA
  17. 17.  VISCERAL FAT  CYTOKINES INHIBITED CURCUMIN  BOSWELLIA  ANTI OXIDANTES
  18. 18. Stress oxidativo  Medir mda
  19. 19. CHRONIC STREES CORTISOL GLICOGENOLYSIS RISE BLOOD SUGAR (IF NOT CONSUME BY CELLS – INSULIN RESISTANCE) GLICEROL 3 – PHOSPHATE DESHIDROGENASE CR V PPAR FATTY ACIDS RESISTIN ADIPONECTIN INCREASE ADIPOCITE
  20. 20. CHRONIC STRESS DECREASE AFTENOON CORTISOL TO EXAUSTION (CIRCADIAN RYTHM) GLICOGENOLYSIS HUNGER BY HHA ACHT LOW CORTISOL RESPONSE INCREASE COMPULSION OF CARBOHIDRATES
  21. 21. CORTISOL SEROTONIN TRIPTOPHANE DHEA TESTOSTERONE DISBIOSIS 5HTP SEROTONINE
  22. 22. Flora bacteriana intestinal  Disbiose  Ph da saliva  Transito intestinal  hipocloridria
  23. 23. CORTISOL INTRACELULAR LEVEIS OF ZN ZN CORTICAL REGION (SUPRARRENAL) ZN 5 BETA REDUCTASE (LIVER) BOTH CREATE AND DESTROY CORTISONE
  24. 24. CORTISOL BIOAVABILITY OF ZN TESTOSTERONE LOW ACTIVITY OF 5 ALFA REDUCTASE 5DHT(DECREASE) AROMATASE(INCREASE)
  25. 25. STRESS ZN DEPENDENT SE T4 2-5 T3 EUTHYROID SICK SYNDROME DIODINASE DECREASE
  26. 26. stress  Medir stress adrenal
  27. 27. DIET: PROTEIN CARBOHIDRATES FAT MICRO AND MACRONUTRIENT FOOD MODULATORS BEST?
  28. 28. PHYSICAL ACTIVITY PLEASURE (STRESS-OBESITY) EXCESS
  29. 29. NUTRITIONAL THERAPY FOR PHYSICAL ENDURANCE CREATINE NADH CARNITINE COQ10 D – RIBOSE WHEY PROTEIN COQ10 GLUTAMINE BCAA
  30. 30. Dieta ken
  31. 31. Only protein diet has been used successfully to prevent loss of lean body mass first in post- surgical and then in obese patients. We studied overweight and obese patients receiving short treatments of an exclusively protein-based nutritional solution as 24-hour enteral infusion. Methods: 19,036 patients (age 44.3 ± 13, M:F = 2:5) with an initial body mass index of 36.5 ± 7.1 underwent 10-day cycles of enteral nutrition through a fine nasogastric tube. The nutritional solution consisted solely of 50–65 g of proteins, plus vitamins and electrolytes. Conclusion: KetogenicEnteral Nutrition treatment of over 19,000 patients induced a rapid 10% weight loss, 57% of which was Fat Mass. No significant adverse effects were found. The treatment is safe, fast, inexpensive and has good one-year results for weight maintenance.
  32. 32. The 24-hour infusion was controlled with a small portable pump. Before and after each 10-day cycle body composition was checked with a Handy 3000 impedance analyzer. At the onset of treatment, average fat mass was 40.9 ± 12.8 kg while body cell mass was 42.7 ± 7.2 kg in males and 27.4 ± 4.6 kg in females. Results: After an average of 2.5 cycles the patients lost 10.2 ± 7.0 kg of body weight, 5.8 ± 5.5 kg of fat mass and 2.2 ± 3.3 kg of body cell mass. No significant adverse effects were recorded except asthenia and constipation which were easily controlled with therapy. Long-term results were obtained from 15,444 patients and after an average of
  33. 33. Conclusion: KetogenicEnteral Nutrition treatment of over 19,000 patients induced a rapid 10% weight loss, 57% ofwhich was Fat Mass. No significant adverse effects were found. The treatment is safe, fast, inexpensive and hasgood one-year results for weight maintenance.
  34. 34. Table 2 (g%) Composition of the nutrition powder (K1000W) Proteins 90.0 Carbohydrates 1.80 Fats 0.80 Calcium 0.40 Potassium 1.00 Phosphorus 0.20 Sodium 0.10 Magnesium 0.05 Table 2 Composition of K1000W (Nutrimed 2000 srl, Italy), the nutrition feed used for the KEN, made of whey proteins enriched with potassium chloride,
  35. 35. However, the KEN diet differs from the PSMF diet in several key points;[17] ● Protein intake is supplemented continuously both day and night via infusion through a small nasogastric tube. This ensures a steady protein intake at all times, avoids the unpleasant taste of less-palatable proteins and allows a more effective control of protein intake. ● Daily protein intake is reduced to 50 g for women and 65 g for men (an average of 0.86 g/kg of ideal body weight) considering that we are using only high biological value protein. Furthermore, with a slow-flow tube infusion (2.1-2.7 g of protein/h) we can suppose 100% intestinal absorption. ● Carbohydrate intake is completely eliminated; during each treatment cycle patients are permitted to drink only water or tea without sugar. ● Length of treatment is reduced to a 10-day cycle. Patients can repeat
  36. 36. ● Daily protein intake is reduced to 50 g for women and 65 g for men (an average of 0.86 g/kg of ideal body weight) considering that we are using only high biological value protein. Furthermore, with a slow-flow tube infusion (2.1-2.7 g of protein/h) we can suppose 100% intestinal absorption.
  37. 37. ● Carbohydrate intake is completely eliminated; during each treatment cycle patients are permitted to drink only water or tea without sugar. ● Length of treatment is reduced to a 10-day cycle. Patients can repeat multiple cycles after a rest period of at least 10 days
  38. 38. Treatment complications: Asthenia 24% Mild sense of hunger 12% Constipation (need to increase Macrogol) 5% Problems with the pump 4% Damage of the external part of the tube (e.g., shaving) 2% Gastric hypersecretion 2% Nausea and vomiting 1% Intolerance to the nasal tube 0.03% Ulcerations or bleeding due to the tube not observed Breakage of the tube in esophagus or in the stomach not observed Perforation or bleeding of the stomach not observed
  39. 39. In principle, only 3 categories of patients cannot be subjected to KEN: a) Patients who cannot take a normal amount of protein. The KEN provides the administration of 60-80 grams of protein a day, when the amount that would normally be assumed corresponds to a gram of protein per kilogram of body weight (that is a much greater quantities). But there are patients with kidney failure that are forced on diets which are low in protein, including low-protein pasta and bread. These patients cannot categorically be included in the treatment with KEN. b) b) Patients allergic to milk proteins. The solutions that we commonly use are proteins derived from milk. Those who are allergic to milk proteins and are prone to skin irritation due to dairy intake cannot be possibly subjected to the KEN with the usual protein solutions. They must use alternative types of protein solutions, although these have a higher cost. c) c) Patients less than 14 years old. Diets below this age are likely to induce severe alterations that might lead to anorexia.
  40. 40. Introduction of the NasogastricTubeIt is necessary to slowly infuse the solutions of protein during the 10 days cycle. There is no need for preparation and the patient may have taken food or fluids immediately before the introduction. Patient during the introduction of the tubeThe patient is seated and will be asked to sip water with a straw while the thin tube is inserted into the nose. The procedure takes a few seconds and is not painful. Having said that, and during the first 10 minutes, the patient might experience some uncomfortable sensation in the nose and throat due to the foreign object which was introduced. This feeling gradually disappears as the body gets used to the presence of the tube. From then on, and for 10 days, the patient should not take anything but water, tea, chamomile tea or coffee without sugar or sweeteners, otherwise the Ketones are reduced and the feeling of hunger might appear. This is something which should carefully be avoided.
  41. 41. ObesityandWeightLoss The Nine Pillars of Successful Weight Loss that should not be overlooked if healthy weight management is to be achieved are: • Restore insulin sensitivity • Restore youthful hormone balance • Control rate of carbohydrate absorption • Increase physical activity • Restore Brain Serotonin/ Suppress Hunger Signals • Restore resting energy expenditure rate • Restore healthy adipocyte (fat cell) signaling • Inhibit the lipase enzyme • Eat to live a long and healthy life
  42. 42. Insulin Resistance and/or LeptinResistance In addition to being a result of obesity, elevated levels of the hormones leptin and insulin in obese individuals may be indicative of a resistance to their activities. Insulin is a hormone that helps facilitate cellular uptake of glucose, primarily in the muscles, liver, and adipose tissue. Moreover, while higher levels of both leptin and insulin normally suppress the desire to eat and stimulate energy expenditure, they are unable to perform this function in resistant individuals (Hagobian 2010). Insulin resistance is a consequence of sustained hyperinsulinemia (high insulin levels) and is complicated by chronic inflammation and obesity (Sung 2011; Ortega Martinez de Victoria 2009; Weisberg 2003). Strategies aimed at improving insulin sensitivity are an integral part of the nine pillars of successful weight loss. These strategies can include use of a low-cost prescription drug called metformin, which is approved for the treatment of type 2 diabetes and can also help reduce body fat, and natural compounds that help promote healthy insulin signaling (see below) (Despres 2003; Berstein 2012). Similarly, leptin resistance results from sustained periods of high leptin secretion associated with high fat stores. In obese individuals, leptin may lose its ability to be transported into the brain (Jequier 2002). An interaction between leptin and the inflammatory biomarker C-reactive protein (CRP) in cell culture suggests a role of chronic inflammation in leptin resistance and the loss of appetite control. compound curcumin and omega-3 fatty acids from fish oil, may help combat the detrimental effects of leptin resistance (Yu 2008; Shao 2012; Selenscig 2010; Tsitouras 2008). In addition, the mango-like fruit of Irvingiagabonensis, a tree found in Africa, has also been
  43. 43. Sex Hormone and Thyroid Hormone Insufficiencies/ Imbalances Levels of sex hormones (such as testosterone and dehydroepiandrosterone [DHEA]) decline with age in both genders. This may lead to an increase in fat mass, reduction in lean body mass or central fat redistribution (Apostolopoulou 2012; Villareal 2004). Similarly, declining thyroid hormone levels are associated with reduced metabolic rate and thus obesity (Biondi 2010). In men, free testosterone levels sharply declines between the ages of 40 and 80. Both free and total testosterone levels are significantly lower in overweight and obese men compared to those with weights in a normal range across all ages (Wu 2008). Men with low testosterone levels (hypogonadism) develop increased fat mass, and testosterone replacement therapy in hypogonadal men reduced fat mass by 6% in one study (Mårin 1995; Kaufman 2005).
  44. 44. Obesity and low testosterone have a complex relationship; low testosterone can be considered both a cause andconsequence of obesity (Wu 2008). In men, increases in fat mass may also increase the conversion of testosterone toestrogen by the enzyme aromatase (Vermeulen 2002). While this conversion is a normal phenomenon, aromatization occurs more readily in fat tissue, and is increased by obesity, age, inflammation, insulin, leptin, and stress (Williams 2012).
  45. 45. Thus, in older men with excessive abdominal fat, the ratios of testosterone to estrogen are lower than in younger men. Elevated estrogens, similar to low testosterone levels, are associated with increased abdominal fat (Vermeulen 2002). If a blood test reveals elevated estrogen (estradiol) levels in a man, a physician may prescribe an aromatase-inhibiting drug such as anastrozole (Arimidex®). In women, estrogen levels decline suddenly with menopause. Hormone replacement has shown modest increases in lean body mass and reductions in waist circumference and abdominal fat in some, but not all studies of post-menopausal women (Salpeter 2006; Mayes 2004; Norman 2000).
  46. 46. The thyroid is a central regulator of metabolism; it integrates signals from the brain and secretes thyroid hormone (thyroxine or T4) to influence metabolism in a variety of tissues (Biondi 2010). Thyroid dysfunction can affect body weight and composition, body temperature, and energy expenditure independent of physical activity. Depressed thyroid function (hypothyroidism) has been associated with decreased thermogenesis (conversion of stored energy into heat) and metabolic rate, and weight gain (Biondi 2010). Clinical studies have shown that treatment of hypothyroidism with thyroxine may lead to weight loss, and population studies suggest that low T4 levels and high TSH levels are both associated with higher BMI (Asvold 2009). Depressed thyroid activity is also
  47. 47. HCG  First discovered by Ascheim and Zondek as back as 1927 in the urine from pregnant women (2,67), thousands of articles were published regarding its action on gonads, but comparatively quite a few investigated its vast therapeutics potentialities, encompassing Kaposi sarcoma (33,42,49,77), asthma (63,66), mood and psychiatric disorders (22,23,28,60), artheriopaties (14), thalassemia (7,19,56), osteopenia (56), glaucoma (53).  hCG is the glycoproteic hormone normally secreted by trophoblastic cells of the placenta during pregnancy (67).  It consists of two dissimilar,
  48. 48. HCG  The three pituitary hormones  LH (Luteinising Hormone), FSH (Follicle Stimulating Hormone) and  TSH (Thyroid Stimulating Hormone)  are closely related to hCG in that all four are glycosilated and have a dimeric structure comprising the alpha and beta chains as well.  The aminoacid sequence of alpha chain of all four human glycoproteic hormones is nearly identical (58).  The aminoacid sequence of the Beta subunits differs and account for by the unique immunological and biological activities of each glycoproteic hormone (62).  Beta hCG contains a carboxylic residue of 30 aminoacids characteristic to hCG (11,51)
  49. 49. The first report on hCG and obesity was published back as 1954 in The Lancet, by a British physician, Dr. A.T.W. Simeons (70,71). After its publication, hCG was advocated for several years as a useful approach to obesity. The pendulum of its popularity swinged back and forth until a serial of studies (1,3,8,17,35,50) but five (3,20,24,80,80b) concluded hCG was of no use to manage the disease
  50. 50. Simeons ATW.: The action of chorionic gonadotropin in the obese. Lancet II: 946-947. 1954
  51. 51. HCG  This is a glycoprotein hormone that can melt abnormal fat banks in the body and accelerate metabolism. Obese people, who want to get rid off bulges and flabby muscles can consume or inject this hormone for a dramatic weight reduction. To lose 40 lbs and more, one has to undergo 44 days of Hcg weight loss program.
  52. 52.  Hcg treatment for obesity really works because in this diet plan an overweight individual have to maintain a VLCD protocol for 44 days.  This hormonal therapy comes with the combination for 500 calorie diet and 125 i.u. of daily Hcg dose.  It will shed 1-3 lbs in just one day!Hcg drops or injections burns out the abnormal fat deposit in the body and release calories from them.  It accelerates metabolism.  No pain and muscle cramps  Taken under the tongue  Required no mixing  The drops do not have an expiry date  A great shelf life  The diluted hormone acts faster as it dissolves 10 to 48 drops will shed 1-3 lbs in 24 hours!
  53. 53. The Three Stages of HCG Protocol are:  Load days: In this period, the patient is allowed to consume high fat containing foods so that during the low calorie days they may not go into starvation mode. One thing has to be ensured that high fat does not accompany high sugar and high cholesterol.  VLCD: VLCD follows the load days.  It stands for Very Low Calorie Diet.  This is the period when people shed weights.  During these days, people need to follow very low calorie diet.  Their meals have to be planned so that these don’t contain more than 500 calories.  With low calorie diet, the patients take HCG drops or injections.  In the last three days of the period, the diet is maintained but the HCG is stopped.
  54. 54. The Three Stages of HCG Protocol are:  Maintenance (M1 & M2): During the last period of protocol, the body’s metabolic rate has to be stabilized and set point weight has to be created.  In the first three weeks (M1) of this stage, one must consume 1500 calories per day.  In the final stage (M2), more starch and sugar is added to the diet.  To maintain healthy body throughout the life, one has to follow the healthy life style.  His duty doesn’t stop after the completion of the HCG course. He should always follow a proper diet system.  He should practice some exercise so that he doesn’t gain extra weight again in his life.  Always avoid alcohol and other intoxicants.  These may be hazardous to health.HCG drops are available in injection and oral drop forms.  The drops are very much popular than the injections as it doesn’t involve pain.  The drops are taken under the tongue and as it is in the diluted form, it gets dissolved in the blood very quickly.
  55. 55. TEST STANDARD REFERENCE RANGE OPTIMAL LEVEL Thyroid-stimulating hormone (TSH) 0.4 – 5.0 µIU/mL 1.0 – 2.0 µIU/mL Free thyroxine (T4) 0.82 – 1.77 ng/dL Upper third of reference range Free triiodothyronine (T3) 2.0 – 4.4 pg/mL 3.4 – 4.2 pg/mL Total cholesterol 100 – 199 mg/dL 160 – 180 mg/dL LDL cholesterol 0 – 99 mg/dL <100 mg/dL HDL cholesterol >39 mg/dL >50 mg/dL Triglycerides 0 – 149 mg/dL <80 mg/dL Sex hormone binding globulin (SHBG) Men Age 20 – 49: 16.5 – 55.9 nmol/L Age >49: 19.3 – 76.4 nmol/L 30 – 40 nmol/L Women Age 20 – 49: 24.6 – 122 nmol/L Age >49: 17.3 – 125 nmol/L 60 – 80 nmol/L Dehydroepiandrosteron e sulfate (DHEA-S) Men Age 20 – 24: 211 – 492 µg/dL 350 – 490 µg/dL Women Age 20 – 24: 148 – 407 µg/dL 275 – 400 µg/dL
  56. 56. Total testosterone Men 348 – 1197 ng/dL 700 – 900 ng/dL Women 8 – 48 ng/dL 35 – 45 ng/dL Free testosterone Men Age 20 – 29: 9.3 – 26.5 pg/mL 20 – 25 pg/mL Women 0.0 – 2.2 pg/mL 1 – 2.2 pg/mL Estradiol Men 7.6 – 42.6 pg/mL 20 – 30 pg/mL Women Premenopausal: varies Postmenopausal: <6.0 – 54.7 pg/mL Premenopausal: varies Menopausal/ postmenopausal: 30 – 100 pg/mL Progesterone Women Premenopausal: varies Postmenopausal: 0.1 – 0.8 ng/mL Premenopausal: varies Menopausal/ postmenopausal: 2 – 6 ng/mL C-reactiveprotein (high sensitivity) Low risk: ≤1.0 mg/L Men <0.55 mg/L Women <1.0 mg/L
  57. 57. Insulin 2.6 – 24.9 µIU/mL <5 µIU/mL Glucose (fasting) 65 – 99 mg/dL 70 – 85 mg/dL Blood Pressure (optimal) ≤120 / 80 mmHg 115 / 75 mmHg
  58. 58. Overeating and Dining Out Increases in daily average food consumption significantly contribute to weight gain in the United States (Swinburn 2009). Data from the National Health and Nutrition Examination Survey (NHANES) show a significant increase in average daily energy intake between 1971 and 2000, amounting to 168 calories per day for men, and 335 calories per day for women. Without increased expenditure, this represents potential theoretical weight gains of 18 pounds per year for men and 35 pounds per year for women (Hill 2012). A separate study estimates a 350 calorie per day increase for children (about one can of soda and a small order of French fries) and a 500 calorie per day increase for adults (about one large hamburger) over our daily calorie intake in the 1970s (Swinburn 2009). People have a decreased ability to make healthy food choices away from home for several reasons. They tend to increase their consumption proportional to the amount of food they are served, and average portion sizes have been steadily increasing over the last 30 years (Rolls 2006; Nielsen 2003). Choices for foods consumed away from home are also influenced by marketing, and the relative abundance of high-calorie, low-nutrient choices compared to healthier ones. Fast food restaurants may also play into inherent weaknesses in human cognitive capacity. Reasoned decisions are time-consuming; therefore, people often depend on automatic choices when they are hungry. When glucose levels are low, or a person is distracted or preoccupied, they tend to make less healthy food choices and are often unaware of the quality of food they have consumed.).
  59. 59. In an effort to avoid the caloric excess to which so many restaurant-goers succumb, suppression of hunger signals is likely to be of great benefit. To this end, several natural compounds, including saffron extract, L-tryptophan,, as well as the pharmaceutical drug lorcaserin (Belviq®) may be of benefit; each of these compounds is discussed in detail later in this protocol. Another strategy to counter the excessive amount of calories encountered when dining out involves “preparing your body to eat” by taking measures to reduce the rate at which fats and carbohydrates are absorbed. Supplementing withgreen coffee extract before meals can slow carbohydrate absorption, helping to reduce after-meal spikes in glucose levels (Vinson 2012). These after-meal glucose spikes inflict damage to cells via multiple mechanisms and have been linked to cardiovascular disease, cancer, Alzheimer’s disease, and kidney failure. Also, a pharmaceutical drug calledorlistat(Alli®, Xenical®) can help reduce the absorption of fats by inhibiting an enzyme called lipase (see below) (McClendon 2009; Smith 2012). Targeting after-meal spikes in blood levels of glucose (postprandial glycemia) and fatty acids (postprandial lipemia) is a critical step towards averting cardiovascular disease, for which obesity is a leading risk factor (Blaak 2012; Strojek 2007; Sahade 2012; Jackson 2012). Altered Serotonin Signaling, Chronic Stress, and Appetite Low levels of the neurotransmitter serotonin, typically associated with depression, may be associated with weight gain. Serotonin interacts with receptors in the brain that regulate feeding behavior (Sargent 2009). When brain levels of serotonin are increased, the desire to eat is decreased; as serotonin levels drop, appetite is stimulated (Lam 2010). Mimicking the serotonin-receptor interaction has been the target of several anti-obesity drugs developed over the last 4 decades (Ioannides-Demos 2011). Moreover, studies have shown that obese individuals have low levels of tryptophan, a
  60. 60. Obesity: nutrients modulators of neuropeptides and neurotransmmitters
  61. 61. What Are Neurotransmitters? Neurotransmitters serve as messengers, transmitting information from one nerve cell to another  Deficits in specific neurotransmitters disrupt the sleep cycle  It is important to support healthy neurotransmitter function when addressing sleep disturbance http://www.ninds.nih.gov
  62. 62. naltrexone  As of May 2004:In preparing a proposed clinical trial protocol for the use of LDN in the treatment of multiple sclerosis, Dr. Bihari assembled the latest data from his clinical practice. As of May 2004, Bihari has almost 400 patients with MS in his care. Of that group he knows of only two patients who showed signs or symptoms of new disease activity over the years while taking LDN treatment. One was a 41-year-old woman who, after 18 months on LDN, had an episode of optic neuritis which cleared in 4 weeks. The other was a patient who, after 8 months on LDN, had an episode of numbness in the left leg that had not been experienced previously and which cleared after 3 weeks.
  63. 63. naltrexone  As of March 2002:Clinically the results are strongly suggestive of efficacy. Ninety-eight to 99% of people treated with LDN experience no more disease progression, whether the disease category is relapsing-remitting or chronic progressive. Dr. Bihari has more than 70 people with MS in his practice and all are stable over an average of three years. The original patient on LDN for MS, now on it for 17 years, has not had an attack or disease progression for 12 years since the one missed month that led to an attack.
  64. 64. Inhibitory •Seroton in •Gaba •Taurine •Glycine
  65. 65. Excitatory •Epinephrine •Norepinephrine •Dopamine •Glutamate •Phynylethylamine (PEA)
  66. 66. Excite & Inhibit •Serotonin can be both excitatory and inhibitory
  67. 67. The Most Common Deficiency SEROTONIN
  68. 68. Serotonin Deficiency •Carbohydrate cravings •Migraine •Premenstrual syndrome •Depression •Insomnia •Obsessive-compulsive •Panic attacks
  69. 69. Serotonin Precursors •Tryptophan •5-htp-5 hydroxitryptophan •Grifonia •saffrin
  70. 70. Serotonin Herbs •St. John’s wort •Rhodiola
  71. 71. LEVELS OF SEROTONINE GRIFFONIA 5 HTTP TRYPTOPHANE DRUGS: SISR (SELETIVE INHIBITORS OF SEROTONINE REUPTAKE)
  72. 72. Dopamine Deficiency •Sugar/caffeine cravings •Fatigue, Lightheadedness •Pallor •Diarrhea •Decreased libido •Routine-task difficulty •Decreased physical activity •Low mood
  73. 73.  LOW DOPAMINE PHENYLALANINA  TYROSINE MUCUNA EuPHORIA  CAFFEIN BLOCK DOPAMINE ADENOSINE TIRED
  74. 74. Dopamine Precursors •Tyrosine •CAFEINA •D,L – phenylalanine •Mucuna •GING SENG
  75. 75. Figure 1. Dopaminergic pathways. (a)Dopaminergic pathways. PFC, prefrontal cortex; CG, cingulate gyrus; OFC, orbitofrontal cortex; NAcc, nucleus accumbens; Amyg, amygdala; STR, striatum; TH, thalamus; PIT, pituitary; HIP, hippocampus; VTA, ventral tegmental area; SN, substantia nigra. (b) Increases in dopamine in nucleus accumbens induced by food and by amphetamine as assessed by microdialysis in rodents. Graphs modified from ref. 60. Dopamine is stimulated by food and amphetamines.
  76. 76. Epinephrine Excess •Anxiety •Hyperactivity •Stress •Carbo eating
  77. 77. Norepinephrine Deficiency •Fibromyalgia •Mood disorders • salt craving •PMS •Very strenuous exercise
  78. 78. Epi-norepi precursors  Phenylalanine  Mucuna  tyrosine
  79. 79. TYROSINE DOPAMINE TRYPTOPHAN GLUTAMINE GABA 2. Each individuals health benefits from having the right molecules in the right amounts. MELATONIN SEROTONIN 5-HYDROXY- TRYPTOPHAN NOREPI- NEPHERINE EPI-NEPHERINE SaMe Theanine, Taurine C,B6,Ca Theanine
  80. 80. Gaba functions •Modulates orther neurotransmitters •Calms the brain rhythms •Induces alpha brain waves
  81. 81. Gaba Deficiency Symptoms •Flushing •Tachycardia, Palpitations •Trembling, Twitchy •Cold, Clammy hands •Carbohydrate cravings •Lump in the throat •Ununsual tastes, odors
  82. 82. Gaba precursors  Theanine  Kava kava  Taurine  Glutamine  Benzodiazepines  Valeriane  passiflorine
  83. 83. THEANINE GREEN TEA “Theanine, when reaching the brain, has been shown in rats to increase both serotonin and dopamine production.4 “Regardless of the mechanism, theanine increases alpha-brain wave activity, a sign of induced relaxation.”6” “Theanine also inhibits the efflux of chemotherapeutic agents, such as doxorubicin, idarubicin, cisplatin, and irinotecan, causing them to accumulate in tumor cells. Theanine also protects normal cells from damage by these drugs via antioxidant activity, specifically by maintaining cellular GSH levels.7-10” Page 136 Alternative Medicine Review ◆ Volume 10, Number 2 ◆ 2005 ARTICLE BELOW Theanine works on serotonin and dopamine.
  84. 84. Neutopeptides and Obesity Hungry Hypothalamic Satiety Nucleus
  85. 85. Leptina => with gaining weight Produced by Direct Relationship Gene OB With loosing weight Fatty Cells slow relationship=gaining weight
  86. 86. (Biochim. Biophys. Acta 2005 May 30; 1740 (2) 293- 304 Leptine => Inhibits NPY(neuropeptide Y)=> Levels Leptine Empty Stomach Intolerance (resistance) Hunger Modulate by 5HTP
  87. 87. Resistina=> weight => insulin resistance Adiponectina => weight => insulin sensibility Modulation: Food glicemic index Chromium, vanadium PUFA Protein Metphormin Omega 3 (arteriosclerosis, thromb and vascular bioloy 2007)
  88. 88. NPY=> Neuropeptide Y 36 amino acids peptide anabolic effectors (hungry) inhibits thermo genesis During fasting After eating
  89. 89. NPY Modulators  Slow absorbing foods  5HTP  Protein Supplement  Drugs that increase shtp recaptation •Protein •Fatty Acids •Complex Carbohydrates
  90. 90. Peptide YY (PYY) is secreted from the endocrine L cells of the small and large bowel, and release into the circulation after meals. PYY is a member of the neuropeptide Y (NPY) family with a tyrosine residue at both ends. Peripheral administration of PYY 3-36 leads to marked inhibition in food intake. In human volunteers, an exogenous infusion accurately mimicking postprandial PYY 3-36 concentrations reduced food intake by 30% when compared with saline control in a double-blinded cross-over study with no adverse effects. Peptide YY
  91. 91. MODULATION OF PPY  FOOD PROTEIN AND COMPLEX CARBOHYDRATES  INCREASING CCK  ADMINISTERING AMINOACIDS OR PEPTIDES
  92. 92. “Marijuana and its major psychotropic component, 9- tetrahydrocannabinol, stimulate appetite and increase body weight in wasting syndromes,” “ The endocannabinoid system controls food intake via both central and peripheral mechanisms, and it may also stimulate lipogenesis and fat accumulation.” Di Marzo V. & Matias I. Endocannabinoid control of food intake and energy balance Nature Neuroscience 8, 585 - 589 (2005) ARTICLE BELOW http://isdt.ius m.iu.edu/mar ijuana.htm Don’t Smoke Pot or anything else.
  93. 93. Cannabinoides (Modulators)  Rimonabant  Pholia Magra (Boraquinaceas family) (Pau-de-vira-tripa means high and skinny person)
  94. 94. CCK=> Cholecystokinin=> released by the GI system close pylori sphincter keeps longer time food in stomach inhibit NPY Is destroyed by chemotripsine and trypsine in minutes
  95. 95. CCK Modulators  Food rich in protein  Amino acids like phenylalanine and tyrosine  Slendesta (proteinase II inhibitor=> inhibits chimo and tripsina)
  96. 96. Ghreline=> secreted by all cell of the gastric mucose during fasting immediately after eating Neural Control Hunger, digestive secretions and gastrimotility serine estimulates ghreline
  97. 97. Modulators of ghrelin  Amino acids  Slow release food  Bariatric surgery
  98. 98. PPAR => peroxisomes Alfa=Liver heart muscle kidney Gamma => adiposity tissue and macrophages Delta unknown Reduces heavy fatty acids molecules in glycerol => beta oxidation
  99. 99. Modulators  Rosiglitazone  Fibrates  PUFA  CLA  curcumin
  100. 100. Incretines: GPI (Glicose Insulinotropic polipeptide) Releases insuline induced by glicose. Inhibited by DPP4
  101. 101.  Level of incretin rises 60% with feeding in normal patients  Level rises only 6% in diabetics
  102. 102. Modulators  DPP4 Inhibitors: Vildagliptina Sildagliptina  GPI Agonists: exenatide  Nutrients: Irvingia Gambonienses
  103. 103. Cart=> Cocaine and amphetamine regulated transcript Located at the arcuate nucleus Increases hunger ARGININE:NO
  104. 104. CART  Intra-nuclear injection of CART has produced effects different from intracerebroventricular injections. CART injection into PVN, DMN, VMN LH, and Arcuate nucleus produced an increase in feeding after 1 hour of injection. Endocrinology. 2001 Aug;142(8):3457-63. Acute repeated injection of CART 42-89 into the Arcuate nucleus also produces increased food intake. FASEB
  105. 105. Cart  Arginine  Anphetamines  Anphetamines like  5htp
  106. 106. TEST STANDARD REFERENCE RANGE OPTIMAL LEVEL Thyroid-stimulating hormone (TSH) 0.4 – 5.0 µIU/mL 1.0 – 2.0 µIU/mL Free thyroxine (T4) 0.82 – 1.77 ng/dL Upper third of reference range Free triiodothyronine (T3) 2.0 – 4.4 pg/mL 3.4 – 4.2 pg/mL Total cholesterol 100 – 199 mg/dL 160 – 180 mg/dL LDL cholesterol 0 – 99 mg/dL <100 mg/dL HDL cholesterol >39 mg/dL >50 mg/dL Triglycerides 0 – 149 mg/dL <80 mg/dL Sex hormone binding globulin (SHBG) Men Age 20 – 49: 16.5 – 55.9 nmol/L Age >49: 19.3 – 76.4 nmol/L 30 – 40 nmol/L Women Age 20 – 49: 24.6 – 122 nmol/L Age >49: 17.3 – 125 nmol/L 60 – 80 nmol/L Dehydroepiandrosteron e sulfate (DHEA-S) Men Age 20 – 24: 211 – 492 µg/dL 350 – 490 µg/dL Women Age 20 – 24: 148 – 407 µg/dL 275 – 400 µg/dL
  107. 107. Total testosterone Men 348 – 1197 ng/dL 700 – 900 ng/dL Women 8 – 48 ng/dL 35 – 45 ng/dL Free testosterone Men Age 20 – 29: 9.3 – 26.5 pg/mL 20 – 25 pg/mL Women 0.0 – 2.2 pg/mL 1 – 2.2 pg/mL Estradiol Men 7.6 – 42.6 pg/mL 20 – 30 pg/mL Women Premenopausal: varies Postmenopausal: <6.0 – 54.7 pg/mL Premenopausal: varies Menopausal/ postmenopausal: 30 – 100 pg/mL Progesterone Women Premenopausal: varies Postmenopausal: 0.1 – 0.8 ng/mL Premenopausal: varies Menopausal/ postmenopausal: 2 – 6 ng/mL C-reactiveprotein (high sensitivity) Low risk: ≤1.0 mg/L Men <0.55 mg/L Women <1.0 mg/L
  108. 108. Insulin 2.6 – 24.9 µIU/mL <5 µIU/mL Glucose (fasting) 65 – 99 mg/dL 70 – 85 mg/dL Blood Pressure (optimal) ≤120 / 80 mmHg 115 / 75 mmHg
  109. 109. Cancer Obesity is a risk factor for several types of cancer. White adipose tissue (ie, “bad fat”) can secrete a variety of hormones and growth factors that may stimulate cancer cell growth. Experimental cancer models in animals suggest that tumors may recruit healthy cells from elsewhere in the body (including white fat) to build the blood vessels critical for the progression of tumor growth (Zhang 2009).
  110. 110. Postmenopausal breast cancer risk increases with obesity, possibly through effects on systemic inflammation, or increases in circulating insulin and insulin-like growth factor 1 (IGF-1), both of which can promote tumor growth (Brown 2012). Obesity increases gastric and esophageal cancer risk; mechanisms for this also include increased insulin and IGF-1 signaling, as well as increased incidence of gastroesophageal reflux disease (GERD) (Li 2012). Population studies have implicated obesity as a risk factor for liver cancer (hepatocellular carcinoma). Along with obesity, nonalcoholic fatty liver disease (NAFLD), an increase in fat stores in the liver, is a hallmark of metabolic syndrome; the inflammation and liver fibrosis associated with fatty liver can progress into hepatocellular carcinoma (Shen 2012). Central obesity has been reported as a risk factor for colorectal cancer. Comprehensive reviews have estimated that colorectal cancer risk increases by 7% as BMI increases by 2 points, or 5% for each inch of waist circumference above normal (Sung 2011). circulating growth factors and inflammatory cytokines are thought to contribute to the increase in abnormal cell proliferation. Some evidence suggests that the satiety hormone leptin may also play a role in colorectal cancer progression; cell culture studies have shown that leptin can
  111. 111. Obesity may increase thyroid cancer risk; the rise in thyroid cancer incidence parallels that of obesity, although studies that explore the relationship between these two diseases have conflicting results (Fröhlich 2012). The effect of obesity on thyroid cancer may be due to increased insulin/IGF-1 expression; thyroid stimulating hormone levels are sensitive to insulin and IGF-1 levels, and all three hormones work together to stimulate thyroid activity. Increases in IGF-1 have been correlated with increased thyroid tumor diameter, and insulin resistance has been shown to be more frequent in thyroid cancer patients than in cancer- free controls (Mijovic 2011).
  112. 112. Eat for a Long and Healthy Life Caloric restriction. Caloric restriction is the dramatic reduction of dietary calories to a level short of malnutrition (Lane 1998). Restriction of energy intake slows down the body’s growth processes, and causes it to instead focus on protective repair mechanisms; the overall effect is an improvement in several measures of wellbeing. Even in lean, healthy individuals, moderate caloric restriction (22-30% decreases in caloric intake from normal levels) improves heart function, reduces markers of inflammation (eg, C-reactive protein and tumor necrosis factor alpha [TNF-a]), reduces risk factors for cardiovascular disease (eg, LDL-C, triglycerides, and blood pressure), and reduces diabetes risk factors (eg, fasting blood glucose and insulin levels) (Walford 2002; Fontana 2004, 2006; Meyer 2006). The multicenter CALERIE trial on the effects of calorie-restricted diets in otherwise healthy, overweight volunteers has shown that moderate caloric restriction can reduce several cardiovascular risk factors (LDL-C, triglycerides, blood pressure, and C-reactive protein), in addition to promoting weight loss (Lefevre 2009). It is important to remember that as more calories are eliminated from the diet, dietary levels of essential nutrients drop and may need to be replaced; in studies of 4 popular diet plans that limited calories to 1100-1700 per day (including the NIH and American Heart Association-recommended “DASH diet”), all were found to be on average only 43.5% sufficient in Recommended Daily Intakes (RDIs) for 27 essential micronutrients values, and deficient in 15 of them (Calton 2010).
  113. 113. DIET: PROTEIN CARBOHIDRATES FAT MICRO AND MACRONUTRIENT FOOD MODULATORS BEST?
  114. 114. Dieta ken
  115. 115. Only protein diet has been used successfully to prevent loss of lean body mass first in post- surgical and then in obese patients. We studied overweight and obese patients receiving short treatments of an exclusively protein-based nutritional solution as 24-hour enteral infusion. Methods: 19,036 patients (age 44.3 ± 13, M:F = 2:5) with an initial body mass index of 36.5 ± 7.1 underwent 10-day cycles of enteral nutrition through a fine nasogastric tube. The nutritional solution consisted solely of 50–65 g of proteins, plus vitamins and electrolytes. Conclusion: KetogenicEnteral Nutrition treatment of over 19,000 patients induced a rapid 10% weight loss, 57% of which was Fat Mass. No significant adverse effects were found. The treatment is safe, fast, inexpensive and has good one-year results for weight maintenance.
  116. 116. The 24-hour infusion was controlled with a small portable pump. Before and after each 10-day cycle body composition was checked with a Handy 3000 impedance analyzer. At the onset of treatment, average fat mass was 40.9 ± 12.8 kg while body cell mass was 42.7 ± 7.2 kg in males and 27.4 ± 4.6 kg in females. Results: After an average of 2.5 cycles the patients lost 10.2 ± 7.0 kg of body weight, 5.8 ± 5.5 kg of fat mass and 2.2 ± 3.3 kg of body cell mass. No significant adverse effects were recorded except asthenia and constipation which were easily controlled with therapy. Long-term results were obtained from 15,444 patients and after an average of
  117. 117. Conclusion: KetogenicEnteral Nutrition treatment of over 19,000 patients induced a rapid 10% weight loss, 57% ofwhich was Fat Mass. No significant adverse effects were found. The treatment is safe, fast, inexpensive and hasgood one-year results for weight maintenance.
  118. 118. Table 2 (g%) Composition of the nutrition powder (K1000W) Proteins 90.0 Carbohydrates 1.80 Fats 0.80 Calcium 0.40 Potassium 1.00 Phosphorus 0.20 Sodium 0.10 Magnesium 0.05 Table 2 Composition of K1000W (Nutrimed 2000 srl, Italy), the nutrition feed used for the KEN, made of whey proteins enriched with potassium chloride,
  119. 119. However, the KEN diet differs from the PSMF diet in several key points;[17] ● Protein intake is supplemented continuously both day and night via infusion through a small nasogastric tube. This ensures a steady protein intake at all times, avoids the unpleasant taste of less-palatable proteins and allows a more effective control of protein intake. ● Daily protein intake is reduced to 50 g for women and 65 g for men (an average of 0.86 g/kg of ideal body weight) considering that we are using only high biological value protein. Furthermore, with a slow-flow tube infusion (2.1-2.7 g of protein/h) we can suppose 100% intestinal absorption. ● Carbohydrate intake is completely eliminated; during each treatment cycle patients are permitted to drink only water or tea without sugar. ● Length of treatment is reduced to a 10-day cycle. Patients can repeat
  120. 120. ● Daily protein intake is reduced to 50 g for women and 65 g for men (an average of 0.86 g/kg of ideal body weight) considering that we are using only high biological value protein. Furthermore, with a slow-flow tube infusion (2.1-2.7 g of protein/h) we can suppose 100% intestinal absorption.
  121. 121. ● Carbohydrate intake is completely eliminated; during each treatment cycle patients are permitted to drink only water or tea without sugar. ● Length of treatment is reduced to a 10-day cycle. Patients can repeat multiple cycles after a rest period of at least 10 days
  122. 122. Treatment complications: Asthenia 24% Mild sense of hunger 12% Constipation (need to increase Macrogol) 5% Problems with the pump 4% Damage of the external part of the tube (e.g., shaving) 2% Gastric hypersecretion 2% Nausea and vomiting 1% Intolerance to the nasal tube 0.03% Ulcerations or bleeding due to the tube not observed Breakage of the tube in esophagus or in the stomach not observed Perforation or bleeding of the stomach not observed
  123. 123. In principle, only 3 categories of patients cannot be subjected to KEN: a) Patients who cannot take a normal amount of protein. The KEN provides the administration of 60-80 grams of protein a day, when the amount that would normally be assumed corresponds to a gram of protein per kilogram of body weight (that is a much greater quantities). But there are patients with kidney failure that are forced on diets which are low in protein, including low-protein pasta and bread. These patients cannot categorically be included in the treatment with KEN. b) b) Patients allergic to milk proteins. The solutions that we commonly use are proteins derived from milk. Those who are allergic to milk proteins and are prone to skin irritation due to dairy intake cannot be possibly subjected to the KEN with the usual protein solutions. They must use alternative types of protein solutions, although these have a higher cost. c) c) Patients less than 14 years old. Diets below this age are likely to induce severe alterations that might lead to anorexia.
  124. 124. Introduction of the NasogastricTubeIt is necessary to slowly infuse the solutions of protein during the 10 days cycle. There is no need for preparation and the patient may have taken food or fluids immediately before the introduction. Patient during the introduction of the tubeThe patient is seated and will be asked to sip water with a straw while the thin tube is inserted into the nose. The procedure takes a few seconds and is not painful. Having said that, and during the first 10 minutes, the patient might experience some uncomfortable sensation in the nose and throat due to the foreign object which was introduced. This feeling gradually disappears as the body gets used to the presence of the tube. From then on, and for 10 days, the patient should not take anything but water, tea, chamomile tea or coffee without sugar or sweeteners, otherwise the Ketones are reduced and the feeling of hunger might appear. This is something which should carefully be avoided.
  125. 125. Intermittent fasting  Intermittent fasting (IF) describes diets that cycle between a period of fasting and non-fasting. In some contexts, fasting allows the consumption of a limited amount of low-calorie beverages such as coffee or tea.[1]  Intermittent fasting and caloric restriction are forms of dietary restriction (DR), which is sometimes referred to as dietary energy restriction (DER). Intermittent fasting may have beneficial effects on the health and longevity of animals— including humans—that are similar to the effects of caloric restriction (CR).[2] Specifically, it has been proposed that intermittent fasting improves the cardiovascular and neurological systems.[3] Some studies suggest that benefits could be the result of an overall reduction in caloric intake.[4][5]  Scientific study of intermittent fasting in rats (and anecdotally in humans) has been conducted at least as far back as 1943
  126. 126. Variations One form of intermittent fasting, alternate day fasting (ADF), involves a 24-hour fast followed by a 24-hour non-fasting period. This is sometimes referred to as every other day fasting or every other day feeding. Alternate-day calorie restriction may prolong life span.[7] Modified fasting involves limiting caloric intake (e.g., 20% of normal) on fasting days rather than none at all. A study suggests that this regimen may retain most of the benefits of intermittent fasting.[7] Another form involves eating only one meal per day. In cases that do not restrain consumption, overall calorie intake may increase which worsens some cardiovascular disease risk factors.[8] More generally, forms may choose to specify various ratios of fasting to non- fasting periods. The BBC2 Horizon documentary Eat, Fast and Live Longer [9] covered people who committed to fasting two non-consecutive days per week. Known as the 5:2 diet, people consumed 400–500 calories (women) or 500–600 calories (men) during the days of fasting. During feed days, the diet was regular
  127. 127. Increase Physical Activity Increased physical activity promotes weight loss by addressing both sides of the energy balance equation. It increases energy expenditure leading to reduced body weight and fat mass, and exercise reduces appetite at least in the short term by delaying gastric emptying, or possibly increasing the body’s sensitivity to hormones that control appetite such as cholecystokinin (King 2012). It may also protect against the insulin resistance associated with obesity (Maarbjerg 2011). Several intervention studies in both young (Hebden 2012) and older adults have shown small-to-moderate decreases in body weight, fat mass, and/or waist circumference with regular, moderate exercise (30-45 minutes of moderate exercise, 3-5 times per week), especially when combined with reduced calorie diets. Exercise may also offset some of the lean muscle loss associated with weight loss in older individuals; loss of lean body mass is associated with decreased independence among this group (Stehr 2012). .
  128. 128. PHYSICAL ACTIVITY PLEASURE (STRESS-OBESITY) EXCESS
  129. 129. NUTRITIONAL THERAPY FOR PHYSICAL ENDURANCE CREATINE NADH CARNITINE COQ10 D – RIBOSE WHEY PROTEIN COQ10 GLUTAMINE BCAA
  130. 130. Restore Resting Energy Expenditure Black coffee consumption. Black coffee consumption has been associated with reductions in body weight; it adds fluid to the diet without adding additional calories, and contains compounds (eg, chlorogenic acid and caffeine) that may promote weight reduction (Dennis 2009; Onakpoya 2011). In a large population study of almost 60000 healthy men and women over a 12-year period, coffee consumption was associated with less weight gain in women (Lopez-Garcia 2006). While some of this may have been attributable to caffeine content, the same study also revealed modest associations between greater decaffeinated coffee consumption and less weight gain, suggesting other components of coffee may also protect against weight gain. Intervention studies have reported similarly positive results. In one study, 33 healthy volunteers saw slight reductions of body weight and body fat following 4 weeks of consumption of 750 mL brewed coffee per day that contained both green and roasted coffee constituents (Bakuradze 2011). In a second study, 15 overweight and obese volunteers consumed 11 grams per day of instant coffee enriched with 1000 mg chlorogenic acid (approximately 5 cups coffee per day) for 12 weeks and saw reductions in body weight of almost 12 pounds, compared to a loss
  131. 131. Green tea polyphenols. Green tea has exhibited anti-inflammatory activity in dozens of laboratory and animal studies (Singh 2010), as well as cholesterol-lowering effects in human trials (averaging about 9 mg/dL of LDL cholesterol decrease across 4 studies) (Hooper 2008). The effect of green tea on body composition has been the subject of at least 21 unique trials. Two analyses of these trials suggest a modest effect of green tea on body weight (Johnson 2012; Hursel 2009; Phung 2010). In an analysis of 11 randomized, controlled trials of green tea consumption for 12–13 weeks duration, green tea decreased body weight by about 3 pounds compared to control in Asian participants (Hursel 2009). A second analysis of 15 randomized trials demonstrated that consumption of green tea catechins with caffeine produced a greater decrease in BMI and body weight compared to control (Phung 2010).
  132. 132. Fucoxanthin. Fucoxanthin is a carotenoid from brown seaweed that has been shown to reduce white fat levels in animal models, by increasing energy expenditure through the activation of the thermogenic factor mitochondrial uncoupling protein 1 (UCP1) (Maeda 2005, D'Orazio 2012). In a 16 week trial of 151 obese, pre-menopausal women with and without non-alcoholic fatty liver disease (NAFLD), consumption of a combination of 2.4 mg fucoxanthin and 300 mg pomegranate seed oil, along with a reduced calorie diet (1800 calories/day), resulted in a significant reduction of body weight compared to placebo (an average of 12.1 pounds lost in NAFLD patients and 10.8 pounds lost in non- NAFLD patients) (Abidov 2010). Serum triglycerides and C-reactive protein levels also dropped in both groups taking fucoxanthin/pomegranate seed oil compared to control.
  133. 133. Fish oil. Fish oil, a rich source of the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), can only be synthesized to a limited extent by humans but are nonetheless essential for several metabolic processes. Omega-3 fatty acids have been well studied for the prevention of cardiovascular disease and their ability to lower inflammation and reduce hypertension; these processes are all associated with the progression of obesity and metabolic syndrome (Marik 2009; Geleijnse 2002). Some evidence suggests EPA and DHA may promote thermogenesis (Li 2008). Omega-3 fatty acids from fish oil may have protective effects against weight gain independent of their blood-pressure-lowering and anti- inflammatory roles. When combined with regular aerobic exercise, 6 grams per day of fish oil for 12 weeks demonstrated significantly lowered triglycerides, increased HDL cholesterol, improved endothelium-dependent arterial vasodilation, and improved arterial compliance in a study of 75 overweight volunteers (Hill 2007). Additionally, both fish oil and exercise independently reduced body fat, albeit modestly. Incorporating lean or oily fish, or fish oil into energy-restricted diets (1600 calories per day) resulted in about 2.2 pounds more loss of weight over 4 weeks than diets without fish in a group of 138 overweight and obese men (Thorsdottir 2007).
  134. 134. Capsaicin/ Cayenne. Capsaicin is a major “spicy” constituent of chili peppers (eg, cayenne). Regular intake of chili peppers delays oxidation of serum lipids, which contributes to reducing the risk of cardiovascular disease (Ahuja 2006). Because of the sensation of heat and increased energy expenditure when they are eaten, chili peppers are thought of as potential interventions for obesity management (Luo 2011). Capsaicin has been studied as a potential thermogenic compound in 10 long- and short-term studies, mostly in Asian populations where it is more commonly consumed. Results of capsaicin studies are mixed; it appears to significantly increase energy expenditure (up to 30% in some studies) and decrease appetite and energy intake, but these results are more robust in Asian participants than Caucasians (Hursel 2010). Another compound that may increase resting energy expenditure is 3-acetyl-7-oxo- dehydroepiandrosterone (7-Keto®DHEA).
  135. 135. Restore Healthy Adipocyte (Fat Cell) Signaling Irvingiagabonensis. Irvingiagabonensis is a mango-like West African fruit; extracts of its seeds have been shown to reduce fat stores, and promote healthy blood lipid and fasting blood glucose levels (Egras 2011). Irvingiagabonensisextracts are thought to work by inhibiting adipogenesis (ie, the development of fat cells) by down-regulating a protein involved in activating fat cell growth and proliferation. Three randomized controlled trials have investigated Irvingia extracts in healthy volunteers; all have demonstrated its ability to significantly decrease body fat stores, weight, and waist circumference (Ngondi 2005, 2009; Oben 2008). When compared to placebo, healthy overweight and/or obese volunteers taking 150 mg of Irvingiagabonensis seed extract before meals for 10 weeks exhibited a significantly greater decrease in body fat percentage (6.3% versus 1.9%), body weight (28.2 pounds versus 1.5 pounds), and waist circumference (-6.37 inches versus -2.09 inches), as well as significant drops in total- and LDL-cholesterol, C- reactive protein, and fasting blood glucose (Ngondi 2009).
  136. 136. Sphaeranthusindicus and Mangosteen (Garciniamangostana). Mangosteen has long been used as a diabetic treatment in Southeast Asia; modern investigations suggest antioxidant and anti-inflammatory activities, especially in white adipose tissue (Devalaraja 2011). Sphaeranthusindicus (S. indicus) has been widely used in Ayurvedic medicine for a variety of ailments, and has been studied for its anti- inflammatory, blood sugar-lowering, and lipid- lowering activities in animal and cell culture models (Galani 2010). In a trial of 60 obese volunteers, 30 were randomized to receive 800 mg per day of the S. indicus and mangosteen combination for 8 weeks, while maintaining a restricted 2000 calorie per day diet and exercising (walking) for 30 minutes, 5 times a week. After 8 weeks, the group receiving the dual plant extract exhibited significant reductions in body weight (11 pounds versus 3.3 pounds for placebo), BMI (2.05 versus 0.5 for placebo), waist circumference (4.05 inches versus 2.02 for placebo), as well statistically significant reductions in total cholesterol, serum triglycerides, and serum glucose (Lau 2011).
  137. 137. Control Rate of Carbohydrate Absorption Green coffee extract. Green coffee extract, an antioxidant-rich mixture from unroasted coffee beans, has been shown to temper deadly after- meal spikes in glucose and to combat insulin resistance in animals (Yamaguchi 2008; Ho 2012; Vinson 2012; Nagendran 2011). Higher intakes have been associated with weight loss benefits (Onakpoya 2011).
  138. 138. A study follow-up showed that, contrasting with food-restriction diets, a surprising 87.5% of the test subjects were able to maintain their weight loss after completing the study. No side effects were observed. This and other studies demonstrate the importance of “preparing your body to eat” by taking green coffee bean extract before each meal. The dual effects of reducing after- meal glucose and inducing meaningful weight loss make it a supplement that virtually every aging person should take before eating. In 2011, a detailed review of 3 studies of green coffee extract (180-200 mg per day) for 4-12 weeks in a total of 142 overweight volunteers demonstrated an average reduction in body weight of 5.4 pounds compared to placebo (Onakpoya 2011). A compound called chlorogenic acid may be largely responsible for the weight loss benefits associated with green coffee extract. Chlorogenicacid is not found in great quantities in most conventional coffee beverages, since the roasting process dramatically reduces its content (although methods of retaining or re-infusing chlorogenic acid into roasted coffee have been developed). Chlorogenic acid has been shown to reduce glucose absorption in healthy volunteers (Thom 2007), which may be one way green coffee extract combats weight gain (Shimoda 2006). Moreover, chlorogenic acid may control glucose via inhibition of an enzyme called glucose-6-phosphatase, which is involved in the generation of glucose by the liver through a process known as gluconeogenesis (Arion 1997; Henry-Vitrac 2010). Inhibition of gluconeogenesis may help normalize fasting glucose levels.
  139. 139. L-arabinose. Sucrose (common sugar) is composed of 2 simple sugar molecules, glucose and fructose. It is poorly absorbed in the intestine in this form. In order to be utilized, it must first be broken down by the digestive enzymesucrase. Blocking the enzymatic action of sucrase therefore reduces uptake of sucrose. Researchers have identified a potent sucrase inhibitor called L-arabinose. L-arabinose, an indigestible plant compound, cannot be absorbed into the blood. Instead, it remains in the digestive tract and is eventually excreted (Seri 1996; Osaki 2001). By blocking metabolism of sucrose, L-arabinose inhibits the spike in blood sugar and fat synthesis that would otherwise follow a sugar-rich meal (Osaki 2001). In animal models, L-arabinose virtually eliminated the rise in blood sugar following administration of sucrose, with blood glucose levels rising only 2% higher than in control animals that did not receive sucrose. L-arabinose did not exert any effect on serum glucose levels in control animals that did not receive sucrose (Preuss 2007a). L-arabinose has been shown to be safe in both short- and long-term studies, and may contribute to lowered levels of glycosylated hemoglobin (hemoglobin A1C), a measure of chronic exposure to sugar in the blood. A study concluded that combining L-arabinose and white kidney bean extract not only smoothed out postprandial glucose spikes and reduced insulin levels, it lowered systolic blood pressure as well (Preuss 2007b).
  140. 140. Glucomannan. Glucomannan is a soluble fiber derived from Amorphophalluskonjac. It is thought to prolong gastric emptying time, which has several anti-obesity outcomes. It may increase satiety, reduce body weight, reduce the post-meal rise in plasma glucose, suppress liver cholesterol synthesis, and increase the elimination of cholesterol-containing bile acids (Doi 1995). Doses medias de 300 a 600 mgs An analysis of 14 randomized, controlled studies of glucomannan usage by 531 hyperlipidemic, diabetic, or obese adults and children demonstrated its ability to affect modest reductions in body weight (an average reduction of 1.8 pounds across all studies), when supplied at dosages between 3 and 15 grams per day (Sood 2008). Additionally, glucomannan demonstrated significant average reductions in total cholesterol (-19.28 mg/dL), LDL cholesterol (-15.99 mg/dL), triglycerides (-11.08 mg/dL), and fasting blood glucose (-7.44 mg/dL).
  141. 141. sacietogenicos  Colageno  In cell  Aminoacidos  Whey protein
  142. 142. Restore Youthful Hormone Balance Hormone replacement therapy, using natural compounds like dehydroepiandrosterone (DHEA) and Armour® thyroid, may help aging individuals overcome some of the barriers that insufficient or imbalanced hormone levels pose against successful weight loss. DHEA and 7-Keto® DHEA. Low levels of sex hormones are associated with obesity (Apostolopoulou 2012), as well as systemic increases in inflammatory markers (Singh 2011). Dehydroepiandrosterone(DHEA) is an adrenal steroid hormone, a precursor to the sex steroids testosterone and estrogen. DHEA is abundant in youth, but steadily declines with advancing age and may be partially responsible for age-related decreases in sex steroids (Heffner 2011). DHEA supplementation (50 mg per day for 2 years) in elderly volunteers significantly lowered visceral fat mass and improved glucose tolerance, as well as decreased levels of inflammatory cytokines in a small study (Weiss 2011). High-dose DHEA induced thermogenesis, decreased body fat without decreasing food intake, and decreased glucose levels in animal models; 7-Keto® DHEA (3-acetyl-7-oxo- dehydroepiandrosterone) was shown to be 4-fold more thermogenic than DHEA (Ihler 2003). It may work by increasing the shuttling of energy substrates into the mitochondria for conversion into heat/energy, and may act upon the same enzyme systems as the thyroid hormone T3 (Bobyleva 1997; Ihler 2003). In human studies, overweight volunteers taking 100 mg of 7-Keto® DHEA twice daily lost significantly more weight and body fat than did the placebo group (6.3 pounds versus 2.2 pounds, respectively, and reductions in body fat of 1.8% versus 0.57%) (Kalman 2000). This weight reduction may be related to 7-Keto® DHEA’s effect on increasing resting energy expenditure (REE). In overweight subjects maintained on a calorie-restricted diet, 7 days of treatment with 7-Keto®
  143. 143. Restore Insulin Sensitivity Restoring the function of insulin at the cellular level is paramount to combatting diseases related to chronically elevated glucose levels. Several medical strategies can help accomplish this. Metformin is a blood-sugar-regulating drug used to treat diabetes (Barbero-Becerra 2012); doses ranging from 250 – 850 mg 3 times daily with meals may help facilitate weight loss and promote insulin sensitivity. A physician should be consulted before a metformin regimen is initiated. Restoring youthful levels of testosterone may help men improve their insulin sensitivity as well (De Maddalena 2012). In addition, a number of natural strategies may help improve insulin sensitivity. Chromium. Chromium is an essential trace mineral and cofactor to insulin. Chromium enhances insulin activity and has been the subject of a number of studies assessing its effects on carbohydrate, protein, and lipid metabolism. Magnesium. Magnesium is an essential trace mineral with several potential protective activities against obesity-associated diseases. Population studies suggest a relationship between low magnesium and increased risk of metabolic syndrome and diabetes (Champagne 2008), and a controlled trial has demonstrated its ability to decrease fasting
  144. 144. Inibidores de liberacao de insulina  D-ribose  Opuntia500 mgs  Fasciolamina  metformina
  145. 145. Inhibit the Lipase Enzyme The lipase enzyme is responsible for facilitating the absorption of dietary fats. Taking steps to reduce the activity of the lipase enzyme may reduce the total amount of dietary fat absorbed. The pharmaceutical drug orlistat (Alli®, Xenical®), a lipase inhibitor, is sometimes prescribed by physicians as part of a weight management plan. In addition, the following natural intervention may help control fat absorption. Green tea. Green tea is rich in powerful antioxidants called catechins. Studies have shown that green tea extracts are able to inhibit the activity of the lipase enzyme and reduce absorption of fats from the intestine (Juhel 2000; Koo 2007). In an animal model of obesity induced by a high-fat diet, supplementation with the green tea catechin epigallocatechingallate (EGCG) attenuated insulin resistance and reduced cholesterol levels. Moreover, 16-weeks of treatment with EGCG mitigated increases in body weight, body fat, and visceral fat compared to no treatment. The researchers postulated that these anti-obesity effects may have been conferred in part by a reduction in fat absorption, which was obviated by increased fecal lipid content in animals that received the extract (Bose 2008). Another experiment showed that EGCG reduced the incorporation of lipids into fat cells, suggesting that green tea not only combats fat absorption from the gut, but also acts at the cellular level to combat fat storage (Lee 2009). A similarly designed trial in animals showed that 17 weeks of supplementation with EGCG offset some of the metabolic effects of a high-fat, Western-style diet including body weight gain and symptoms of metabolic syndrome; it also reduced markers of inflammation. Again, these results were partly attributed to reduced fat absorption (Chen 2011). In a human trial among moderately obese subjects, 3 months of supplementation with a green
  146. 146. Eat to Live a Long and Healthy Life Life Extension encourages anyone striving to lose weight to consider adopting a calorie-restricted, but nutrition-dense diet. A detailed explanation of this type of dietary pattern is presented in the Caloric Restriction protocol. Increase Physical Activity Increasing physical activity is one of the most effective means of attaining a negative energy balance, which facilitates weight loss. Physical exercise should be undertaken regularly in accordance with one’s overall health and mobility. Anyone with a physical impairment, such as extreme obesity or severe osteoarthritis, should consult a healthcare provider prior to embarking on an exercise regimen. Restore Resting Energy Expenditure • Green tea extract: 725 – 1450 mg daily with meals • Fucoxanthin: 200 mg three times daily • Fish oil (with olive polyphenols): providing 1400 mg EPA and 1000 mg DHA daily
  147. 147. RestoreHealthyAdipocyte (Fat Cell) Signaling • Irvingiagabonensis: 150 mg twicedaily • SphaeranthusindicusandMangosteen (Garciniamangostana): 800 mg daily RestoreBrainSerotonin / SuppressHungerSignals • L-tryptophan: 500 – 1500 mg daily • Saffronextract: 88 – 176 mg daily • Grafonia 300 a 600 mgs Control Rate ofCarbohydrateAbsorptionand Glucose Synthesis • Green CoffeeExtract as GCATM (std. to 50% chlorogenicacid): 350 mg three times daily (beforemeals) • Seaweedextracts (from Ascophyllumnodosum and Fucusvesiculosus): 250 mg daily • White kidneybeanextract: 445 mg before carbohydrate containing meals: fasciolamina • L-arabinose: 550 mg beforecarbohydratecontainingmeals Pharmaceuticalsupport: Acarbose: 25 – 100 mg beforemeals
  148. 148. RestoreYouthfulHormoneBalance • Dehydroepiandrosterone (DHEA): 15 – 25 mg daily for women; 25 – 75 mg daily for men (dependingonbloodtestresults) • 7-Keto® DHEA: 100 mg twicedaily Pharmaceuticalsupport: • Natural (bioidentical) hormonereplacementtherapy (ifneeded): as directedbyanexperiencedphysician • Thyroidhormonereplacementtherapy (ifneeded): as directed • Aromataseinhibitor (ifneeded; menonly): 0.5 mg twiceweeklyuntil estradiol levels are between 20 – 30 pg/mLofblood RestoreInsulinSensitivity • Chromium: 500 – 1000 mcgdaily • Magnesium: 160 – 800 mg daily Pharmaceuticalsupport: • Metformin: 250 – 850 mg beforemeals (no more thanthree times a day) Inhibitthe Lipase Enzyme • Green teaextract (std. to 98% polyphenols): 725 – 1450 mg daily Pharmaceuticalsupport: • Orlistat (Alli®, Xenical®): 60 – 120 mg beforemeals (no more thanthree times daily) In addition, thefollowing bloodtesting resourcemaybehelpful:
  149. 149. Propolmannan Take at least two hours apart from medications. Because this product may lower blood glucose, consult your healthcare provider before taking this product if you are taking blood glucose lowering medication. Taking fiber products without adequate liquid may increase the risk of choking. Consult your healthcare provider before taking this product if you have difficulty swallowing or esophageal narrowing. DHEA Do not use DHEA if you are at risk for or have been diagnosed as having any type of hormonal cancer, such as prostate or breast cancer. Chromium Because this product may lower blood glucose, consult your healthcare provider before taking this product if you are taking blood lowering medication. Magnesium
  150. 150. Dopamine-Urine (g/gCr) Serotonin- -Urine (g/gCr) GABA -Urine (mol/gCr) Creatinine -Urine (mgdL) 195,3 69,8 21,4 38,6 125-175 175-225 2,0-4,0 N/A 200-500 250-1200 10-15 N/A 57-427 41-275 1,5-35 N/A Patient Results Optimal Range Therapeutic Range Observed Range Laboratory test was performed by Pharmasan Labs, CLIA # 52D0914898; NY Lab PFI # 7426; EIN 39-1841640; Medicare Provider #89065
  151. 151. Lentra ™ Lentra ™ é uma fórmula ansiolítica natural, visando receptores GABA- A. Suporta caminhos que ativam a neurotransmissão inibitória e induz ao relaxamento e serenidade, sem induzir sedação.
  152. 152. Lentra ™
  153. 153. Prolent ™  Prolent ™ é usado em, restauração, e as fases de manutenção inicial para reconstruir ou manter o sistema inibitório de neurotransmissores e ou continuar o apoio inibitório ao reconstruir o sistema excitatório. Use quando função inibitória está abaixo da função de faixa de referência ou serotonina é insuficiente para controlar neurotransmissores excitatórios elevados, especialmente noradrenalina e glutamato.
  154. 154. Prolent ™
  155. 155. Tranquilent ™  Única, mastigável, com sabor de framboesa fórmula fornecendo suporte para o sistema inibitório - tanto serotoninérgica e GABAérgica neurotransmissão. Pode ser usado em situações agudas, bem como para reequilibrar o sistema inibidor. * As doses são adequadas para uso na população pediátrica.
  156. 156. Tranquilent ™
  157. 157. FÓRMULAS EXCITATÓRIAS  Os produtos de apoio excitatórios são projetados para aumentar a produção de catecolaminas, dopamina, noradrenalina e adrenalina, fornecendo precursores essenciais para a via de catecolaminas.
  158. 158. Contegra ™  Contegra ™ é uma fórmula de apoio de amplo espectro para o "fio e cansado", apoiando a produção inibitório e excitatório neurotransmissor, a função supra-renal e da tireóide, e as vias de metilação. Ela também fornece vitaminas do complexo B na coezimáticas e ou forma fosforilada, crítico para a função de neurotransmissor adequada.
  159. 159. Contegra ™
  160. 160. Procite-D™  Procite-D ™ é uma fórmula de apoio visando especificamente catecolaminas dopamina apoiando simultaneamente noradrenalina, adrenalina, endorfina e caminhos- Beta. Ela fornece, em coezimáticas e ou forma fosforilada / desnaturado, vitaminas do complexo B críticos para conversões de neurotransmissores adequados.
  161. 161. Procite-D™
  162. 162. FÓRMULAS DE APOIO Junto com as fórmulas inibitórios e excitatórios de apoio, a linha de produtos TNT ™ também inclui fórmulas para suporte adicional.
  163. 163. SomniTR ™  SomniTR ™ é uma fórmula atrasou- lançado, destinado a liberação de 1 mg de melatonina inicialmente e 1 mg três horas mais tarde, para ajudar a promover a capacidade de permanecer dormindo. SomniTR ™ apoia a produção e os níveis de melatonina através de várias etapas na via serotonina-to-melatonina, e também influencia a atividade inibitória GABAérgica.
  164. 164. SomniTR ™
  165. 165. MethylMax ™  A fórmula de metilação de espectro total para o apoio de todos as principais vias de metilação.
  166. 166. MethylMax ™
  167. 167. Adaptacin ™  A fórmula para os pacientes com necessidade de apoio adrenal. Este produto utiliza a mais alta qualidade, a maioria dos compostos cientificamente validados atualmente disponíveis. Todos os botanicals são padronizados para o máximo de eficácia e são classificados como adaptogens. São utilizadas as formas mais biodisponíveis de nutrientes.
  168. 168. Adaptacin ™
  169. 169. Plenus ™  Plenus ™ é um produto avançado saciedade para enfrentar excessos e perda de peso. Ela representa a vanguarda da pesquisa saciedade por enfrentar a fome através de várias vias distintas, incluindo mensagens gástrico para o cérebro, a função de catecolaminas neural, áreas de fome do hipotálamo, e síntese de ácidos graxos. Plenus ™ é livre de estimulantes como metilxantinas (cafeína, teofilina, teobromina, etc), bem como qualquer botânico oculto ou outra fonte de efedrina e sinefrina.
  170. 170. Plenus ™
  171. 171. WHAT IS THE GOAL • REDUCE OXIDATIVE STRESS • REDUCE VISCERAL FAT • REDUCE LDL OXDIATION • REDUCE INSULIN RESITANCE • INCREASE SACIETY (WITHOUR FOOD DEPENDANCE • REDUCE GLICATION • MODULATE SIRT
  172. 172. WHAT IS THE GOAL  REDUCE BETA AMYLOID TISSUE IN THE BRAIN  REDUCE STRESS AND ADRENAL FATIGUE  INCREASE SACIETY NEUROPETIDES AND NEUROTRANSMITTERS  REDUCE INFLAMMATION (LIKE ENDOTHELIAL  DECREASE MORBI-MORTALITY

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