Obesity: nutrients modulators of neuropeptides and neurotransmmitters

Obesity: nutrients modulators of
neuropeptides and
neurotransmmitters
NUTRIGENOMIC MODULATION OF
OBESITY AS A RISK FACTOR OF SENILITY
DR. EFRAIN OLSZEWER
CMP-FAPES-BRAZIL-2014

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.

Causes of obesity:
 Food: level of carbohydrates
 Stress; cortisol and catecholamine
glicogenolisis
fatty acids
adipocites
 Hypothyroidism
 Sedentarism
 Others (Drugs)

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

Complications of Obesity
 Cardiovascular Diseases
 Rheumatoid Diseases
 Diabetes and complications
 Hypertension
 Stroke, ITA
 Others

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

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

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

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
cafeína.
 Lipolítico: ↑ AMPc pela inibição Catecol-metil
transferase e fosfodiesterase.
 Posologia:350mg-1g

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)

During two weeks,
I diet,
I exercised,
I took my pills and
I lost fourteen dayss.

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

 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 – PHOSPHATE DESHIDROGENASE CR
V
PPAR
FATTY ACIDS RESISTIN
ADIPONECTIN
INCREASE ADIPOCITE

CHRONIC STRESS DECREASE AFTENOON CORTISOL
TO EXAUSTION (CIRCADIAN RYTHM)
GLICOGENOLYSIS
HUNGER BY HHA
ACHT LOW CORTISOL RESPONSE
INCREASE COMPULSION OF CARBOHIDRATES

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 CORTISONE

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

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.

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

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.

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,

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

● 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
multiple cycles after a rest period of at
least 10 days

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

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.

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.

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

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

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).

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).

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).

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

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,

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)

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

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, 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.

 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!

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.

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.

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

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

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

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.).

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

Obesity: nutrients modulators of
neuropeptides and
neurotransmmitters

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

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.

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.

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
•Panic attacks

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 difficulty
•Decreased physical activity
•Low mood

 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 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.

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 right amounts.
MELATONIN
SEROTONIN
5-HYDROXY-
TRYPTOPHAN
NOREPI-
NEPHERINE
EPI-NEPHERINE
SaMe
Theanine,
Taurine
C,B6,Ca
Theanine

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
cravings
•Lump in the throat
•Ununsual tastes, odors

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 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.

Neutopeptides and Obesity
Hungry Hypothalamic
Satiety Nucleus

Leptina => with gaining weight
Produced by Direct Relationship
Gene OB
With loosing weight
Fatty Cells
slow relationship=gaining weight

(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

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)

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 Acids
•Complex
Carbohydrates

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

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 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.

Cannabinoides (Modulators)
 Rimonabant
 Pholia Magra (Boraquinaceas family)
(Pau-de-vira-tripa means high
and skinny person)

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

CCK Modulators
 Food rich in protein
 Amino acids like phenylalanine and tyrosine
 Slendesta (proteinase II inhibitor=> inhibits chimo and tripsina)

Ghreline=> secreted by all cell of the gastric mucose during fasting
immediately after eating
Neural Control
Hunger, digestive secretions and gastrimotility serine estimulates
ghreline

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 fatty acids molecules in glycerol => beta oxidation

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 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

Cart
 Arginine
 Anphetamines
 Anphetamines like
 5htp

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).

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

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).

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).

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

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

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).
.

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

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).

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.

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).

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).

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).

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).

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).

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.

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).

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).

sacietogenicos
 Colageno
 In cell
 Aminoacidos
 Whey protein

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®

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

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 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

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

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

RestoreYouthfulHormoneBalance
• Dehydroepiandrosterone (DHEA): 15 – 25 mg daily for women; 25 – 75 mg daily for men
(dependingonbloodtestresults)
• 7-Keto® DHEA: 100 mg twicedaily
• 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
• Metformin: 250 – 850 mg beforemeals (no more thanthree times a day)
Inhibitthe Lipase Enzyme
• Green teaextract (std. to 98% polyphenols): 725 – 1450 mg daily
• Orlistat (Alli®, Xenical®): 60 – 120 mg beforemeals (no more thanthree times daily)
In addition, thefollowing bloodtesting resourcemaybehelpful:

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

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

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.

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.

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.

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.

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.

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.

FÓRMULAS DE APOIO
Junto com as fórmulas
inibitórios e excitatórios
de apoio, a linha de
produtos TNT ™ também
inclui fórmulas para
suporte adicional.

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.

MethylMax ™
 A fórmula de metilação de espectro total para o
apoio de todos as principais vias de metilação.

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.

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.

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

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

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