The NUTRIGENOMIC

SOLUTION To Reversing
FOOD ADDICTION

Kenneth Blum, PhD1,2, B. William Downs,

B.Sc2 & Margaret A. Madigan, BSn2. roger l.
waite, DC2

Department of Psychiatry, University of Florida

college of Medicine, and McKnight Brain Institute,

Gainesville, Florida, USA
2

Department of Personalized Medicine , LifeGen, inc.,

San Diego, California.

Introduction:
Despite progress that has been made in the treatment of obesity, the prevalence continues
to rise worldwide. While pharmacological treatment of obesity may be effective,
medications may have significant side effects and can be potentially fatal. This booklet will
report on the significant evidence substantiating the existence of Reward Deficiency
Syndrome1 in Obesity and the role of catecholaminergic pathways in aberrant substance
seeking behavior, in particular food cravings. The genetic basis for generalized craving
behavior has been well established. Medical evidence supports the fact that augmentation
with precursor amino acid therapy, enkephalinase and COMT inhibition leading to
enhanced levels of neurotransmitters, such as serotonin, enkephalins, GABA and
dopamine/norepinephrine; and hormones such as leptin, ghrelin, and insulin, will assist in
anti-craving food behaviors.2 A patented KB220Z neuroadaptogen nutraceutical formula
has been show to exert a generalized anti-craving effect and can inhibit food cravings and
carbohydrate bingeing, inducing significant healthy fat loss and relapse (aka yo-yo rebound
weight gain) prevention. The premise for combining sufficient levels of these ingredients
and ingredient complexes is based on solid scientific evidence and specifically designed to
address gene deficits that regulate our mood and motivation to eat. This is the first time the
components of this Symbiotic Diet have been combined, and at the dosage levels
indicated, to promote successful and sustainable body recomposition results and long term
easy-to-achieve maintenance.

The Struggle: to Lose Weight.

For over 30 years of adult life, one of our authors (BD), even though renowned for his
enormous healthy appetite, never worried about weight gain. He was an active athlete and
a nutritional biochemist. He was even involved in weight loss research and writing
scientific papers on the beneficial effects of various nutritional ingredients. He believed he
knew how to stay healthy and control his weight; even though both his immediate and
extended families had a history of obesity and related health problems including diabetes,
heart disease, cancer, and so on. Then, following a year as an Executive VP for a nutritional
products company involving excessive stress and constant air travel, he packed on about
40 pounds of excess fat. He didnt gain the fat during the year of stress and excessive travel,
eating fast food meals on the run, and forfeiting a regular workout routine. He gained
almost all of the excess weight the following year. The thing that bothered him the most
was the feeling of total helplessness as he watched his waistline expand unaffected by his
devoted adherence to conventional weight loss tactics, wisdom, and the best dietary weight
loss supplements money could buy. None of the products or tactics stopped or even slowed
the weight gain momentum until it seemed to hit an irrevocably established plateau at the
increased 40 pound threshold. Thereafter, any success at losing even 3 or 4 pounds was
followed by a 4 to 5 pound increase within a month or two. The quicker he lost it, the
quicker it returned with added fat baggage. Nor could he exercise hard enough or long
enough to reverse the process. Everything he did ultimately seemed to be met with weight

loss rejection. He was losing a frustrating and disheartening battle; a battle in which he
didnt have a choice, and in which all of his educated endeavors were futile. It seemed that
a genetic mandate had finally caught up with him and it was time to pay the piper. For a
number of years, he felt totally helpless to turn it around. Nothing was working; and he was
an informed nutrition professional. He realized this was the exact same frustrating
experience plaguing an ever-growing (pun intended) population of people in America and
worldwide.
Unhealthy weight gain has reached epidemic proportions in industrialized countries
especially in North America. Excess weight conditions are associated with a multitude of
health maladies, like cardiovascular disease, diabetes, high blood pressure, inflammatory
disorders, cancers, and more.3 Our co-author (BD) got even more determined to find the
solution. He began an exhaustive investigation to discover the answer that he knew
existed. All of the research he had done and the science he investigated had value, but had
been on various products in unrelated studies in piecemeal standalone fragments to ensure
commercial value. All of that data needed to be viewed in a combined and organized
manner that addressed the body as a symbiotic whole; not in the isolated fragments. After a
couple of years of diligent investigation he understood the flaw in almost all conventional
weight loss products and tactics was that they tried to force the body to reduce weight
through depriving it of calories (and nutrients) via a number of tactics, or stimulating
metabolism, or stimulating elimination of water and/or waste, or a combination of any of
these. Almost all weight loss tactics cause weight loss in the beginning (usually as water
and lean muscle) and for a period of time; a phase 1 process. But, ultimately, these tactics
are rejected by the body because they create a state of famine; a body unfriendly process.

Phase 2 begins when the bodys response to these energy conserving and seeking tactics
includes a reduction in the basal metabolic rate (rate of calorie burning); an increase in fat
storage; and an increase in appetite, reward cravings, and food seeking behaviors.
The concept of the solution was so obvious that he was stunned by its simplicity. Successful
and sustainable fat loss had to be body friendly, genetically acceptable and not induce the
energy conserving/seeking reactions. Following that premise, he put together a rather
comprehensive picture of biological pathways that needed to be addressed simultaneously,
including energy creation and regulation; stress tolerance and management;
neuroendocrine function, and immune function. But, something was still missingthe role
of the brain and its genetically regulated control of all bodily systems. It was at this time
that Bill Downs fortuitously reconnected with Ken Blum Ph.D. and the missing piece of the
puzzle was found. Dr. Blum discovered the genes responsible for all addictive cravings and
is considered the father of psychiatric genetics and neuro-nutrigenomics. Nutrigenomics is
the field of study that examines the interaction between nutrition and genetics and the
effect of that interaction on human health. Like the Lone Ranger, Dr. Blum came to the
rescue and a new paradigm was born and a real body friendly solution was at hand.
The fight against addictive-type cravings,
especially for food must first take place in the
brain.
The National Institutes of Drug Addiction (NIDA) has recently stated that excessive weight
gain is directly connected to the brains reward center. Genetic instructions drive the
brains control of every bodily function including energy production and regulation, reward

and pleasure cravings, neurological and endocrine function, stress management, and
immune function4,5. The complex interaction of numerous neurotransmitters at the brain
reward site is called the brain reward cascade.6

Figure 1 (A) Schematic represents the normal physiologic state of the neurotransmitter interaction at the
mesolimbic region of the brain. Briefly in terms of the Brain Reward Cascade first coined by Blum and
Kozlowski [6]: serotonin in the hypothalamus stimulates neuronal projections of methionine enkephalin in
the hypothalamus, which in turn inhibits the release of GABA in the substantia nigra thereby allowing for the
normal amount of Dopamine to be released at the Nucleus Accumbens (reward site of Brain). (B) Represents
hypodopaminergic function of the mesolimbic region of the brain. It is possible that the hypodopaminergic
state is due to gene polymorphisms as well as environmental elements including both stress and
neurotoxicity from aberrant abuse of psychoactive drugs (i.e. alcohol, heroin, cocaine, etc). Genetic variables
could include serotonergic genes (serotonergic receptors [5HT2a]; serotonin transporter 5HTlPR);
endorphinergic genes (mu OPRM1 gene; proenkephalin (PENK) [PENK polymorphic 3' UTR dinucleotide (CA)
repeats}; GABAergic gene (GABRB3) and dopaminergic genes ( ANKKI Taq A; DRD2 C957T, DRD4 7R, COMT
Val/met substation, MAO-A uVNTR, and SLC6A3 9 or 10R). Any of these genetic and or environmental
impairments could result in reduced release of dopamine and or reduced number of dopaminergic receptors.
Source: Blum et al (with permission)

The reward cascade involves the release of serotonin, which at the hypothalamus
stimulates enkephalin, which in turn inhibits GABA at the substantia nigra, which then
regulates the amount of Dopamine (DA) released at the nucleus accumbens or the reward
site of the brain. (see figure 2)

Prefrontal
cortex

Reward
pathway -mesolimbic
dopamine
system

VAT

STN

Figure 2. Brain reward cascade showing important brain structures.

Dopamine, a very powerful neurotransmitter in the brain, influences many important
biological functions, including: bone health, neurological wellness, the flow of information
to and from other parts of the brain, voluntary movement, growth hormone, sexual

hormones, analgesic effects, and most importantly here, reward satiety, stress tolerance,
and feelings of well being and happiness.7,8, 9
Under normal conditions dopamine works in the nucleus accumbens (the pleasure center)
to maintain our healthy drives for food, safety, and reproduction.1013 When DA is released
into the synapse, it stimulates a number of dopamine receptors (D1-D5), which results in
increased feelings of well-being and reduced stress.14,, 15 Hence, Dopamine has come to be
known as the pleasure and anti-stress molecule.14,16-24
Stop blaming yourself - from now on blame
your genes
The modern epidemic of overweight is rooted in our evolutionary past in both genetic and
cultural antecedents (factors that came first that exerted influence on obesity). Hereditary
predispositions to overeat, have food and/or sugar cravings and weight gain are shaped
by an interaction of internal forces; biological, genetic, psychological and perceptual, and
external forces; lifestyle comprising mostly environmental and cultural factors. In essence,
overeating and Food (sugar) craving is the result of genetic predispositions that can be
modified by cultural factors. There are many genes that have been associated with elevated
Body Mass Index (BMI), percent body fat, overeating, carbohydrate bingeing, energy
expenditure as well as feeling of satiety (fullness). Although we have not mapped all gene
variants that associate with excessive weight gain, food craving and other related
behaviors, genes play a major role in determining ones body type, fat storage, resting
metabolic rate, energy expenditure and eating behavior, high or low.25,26

This is where what really happens genetically and biologically departs from conventional
weight gain/loss perspectives. Whoever says the reason an overweight person gains
weight or cannot lose it is because they are not disciplined is ignorant about how strong
and determined simple molecular DNA anomalies can be. In contemporary American
society, despite recent advances in our understanding of the biogenetics of overeating, the
condition still carries a stigma. Being overweight is still perceived by many as a symptom of
a character flaw and lack of willpower rather than a biological problem,27-29
Ultimately, as our co-author experienced, being overweight has little to do with will-power.
It is not a character flaw. Dieters may have had the self-discipline to limit food consumption
to grapefruit, watermelon, and cottage cheese; to live on liquid formulas; or to go for
periods of time without eating at all. Some have been so committed to weight loss that they
have even had their jaws wired shut or stomachs stapled. This indicates commitment, selfdiscipline, and motivation. So our message is loud and clear. Stop blaming yourself and
from now on blame your genes.30-31 The information ahead will provide insight into how to
positively influence your gene expression to achieve your health(y) objectives. You cant
change your genesbut, you can change your gene expression; and that can change your
life.
How can our brain make us crave mood
altering substances, including sugar?
Neurotransmitters are the key to our every emotion and behavioral act. Our brain
chemistry could be compromised by a genetic predisposition or through environmental
elements resulting in an impaired BRAIN REWARD CASCADE. To begin, we must

understand how the brain controls eating behavior and what the genetic antecedents to
abnormal food cravings are.
Dopamine works by interacting with five dopamine receptors at nerve cell sites, of which
the dopamine D2 receptor is very important. In 1990, researchers at the University of
Texas System and University of California discovered a specific gene variant associated
with low dopamine D2 receptors and as a result hypo (lower) dopamine function32. The
common genetic hypo-dopaminergic (reduced dopamine receptors) trait was termed
REWARD DEFICIENCY SYNDROME. This genetic anomaly causes a breakdown in the
normal workings of our brains reward cascade33.
The dopamine D2 variant, called the A1 form, has been found in about one-third of the
American population32,34. Thus over 100 million Americans carry the gene for low
dopamine function. Maybe it is a coincidence, but over 1/3 of Americans are defined as
clinically obese. Since everybody needs dopamine for pleasure and its anti-stress qualities,
people with Reward Deficiency Syndrome often seek out unhealthy addictive substances
and behaviors to activate or stimulate nerve cell dopamine release. In fact, it is important to
realize that a low dopamine function may lead to aberrant craving for any substance that
increases dopaminergic activity. Many diverse substances such as alcohol, cocaine, heroin,
nicotine as well as certain impulsive and compulsive behaviors like pathological gambling
and aggression all release dopamine in the brain reward site. What is most relevant here is
that glucose releases dopamine at the same site and in the same manner to achieve a
feeling of well being,35-39 a sort of dopamine fix.

A low number of dopamine receptors limits the beneficial effect of dopamine and can drive
the desire to increase dopamine releaseto get that dopamine fix.40 If you reach for
caffeine, alcohol, cigarettes, ice cream, candy bars, or sugar snacks to feel good and reduce
your daily stress, you are not alone. In the United States, in an average week, we consume 1
billion cups of coffee, 3.4 million cups of tea, 4.5 billion sugared or caffeinated soft drinks,
2.3 billion alcoholic beverages, puff our way through 25 billion marijuana joints, 8.25
billion cigarettes, and pop 1 million ecstasy tabs.41-42
Hunger as defined by Websters dictionary is a strong desire or need for food. In the
overweight person, need and desire for food are two very different feelings. Need
implies supplying nutrients and calories required to sustain life. Desire for food, on the
other hand, implies satisfaction of a wish, dream or pleasure. Need for food would seem to
carry little risk of incidental excess calories as nutritional deficiencies are satisfied.
Satisfying a desire for food on the other hand carries the risk of reckless abandon as one
eats to satisfy a much more elusive calling for pleasure or satisfaction. Without regard for
nutrients, incredible sums of unneeded calories (nutrient deficient calories at that) may be
consumed to alleviate stress and dissatisfaction induced by dopamine deficiency; a
worldwide epidemic.43-47
To add insult to injury, eating a diet of high fat and sugary foods can also result in reduced
numbers of dopamine D2 receptors and lead to compulsive overeating. These are
epigenetic changes in genetic function caused by the environment and do not alter DNA.48
Overeating, including bingeing behavior, does depend on your DNA, and certain genes do
have an impact on the brain reward cascade. A number of investigators have observed a

significant association between the dopamine D2 receptor gene A1 allele and overweight
including: time of onset; carbohydrate preference or craving; high body mass index;
percent of body fat; co-morbid drug abuse; energy expenditure, weight gain, blunted
response to food, and overeating49-58.
The hypothalamus plays a central role in the regulation of energy intake and feeding
behavior. However, the presence of a functional abnormality in the hypothalamus in
humans that may be related to excess energy intake and obesity has yet to be
demonstrated in-vivo (in-the-body research). Functional Magnetic Resonance Imaging
(fMRI) research revealed that the individualized response to sugar in the brain between
obese and lean individuals suggest quite different activities. The obese person apparently
has a blunted or attenuated response to sugar compared to lean individuals. This means
that in genetically predisposed obese-prone individuals (carrying the dopamine receptor
D2 gene TaqI A1 allele) it takes a lot more food consumption to cause a feeling of
satisfaction from good tasting food. These results demonstrate in-vivo, for the first time, the
existence of differential hypothalamic function in lean and obese (or obese-prone) humans
that may be secondary to obesity.59.60
In a recent experiment, a blunted response to food (even to a picture of a chocolate
milkshake) was observed using fMRI in adolescent girls with the A1 form of the D2
receptor. Unlike the controls with normal D2 receptor numbers, the girls with a blunted
response went on to gain weight in the following year.61-63

This trait of low dopamine function is also called dopamine resistance. People with the
greatest genetic predisposition, usually carrying one or more of the genetic risk variants
and have the highest incidence of dopamine resistance.64
Dopamine influences, and is influenced by, many other hormones, enzymes, and
neurotransmitters including: serotonin, enkephalins, endorphins, GABA, COMT, leptin,
ghrelin and insulin. There are many genes other than dopamine that have been identified to
associate with obesity; many of which are working through the brain reward system.65
Most of these genes or the molecular products of these genes interact with dopamine either
upstream (via feedback), downstream (in the sequence of events) or cross stream. As such,
dopamine exerts a systemic influence on many aspects of health. Improving dopamine
sensitivity has many systemic benefits that contribute to reducing unhealthy cravings,
reducing stress; improving focus and concentration; increasing feelings of happiness; and
improving overall health and metabolism; resulting in a healthier regulated brain, a leaner
healthier body; and prevention of relapse.66

What is the Solution?

In about one-third of Americans there is a genetic inadequacy of dopamine sites in the
brain leading to increased desire to consume sugar and food that ultimately sets up an
individual to become over-weight if untreated. We call this genetic abnormality of brain
dysfunction Reward Deficiency Syndrome (RDS).67 The Reward Deficiency Syndrome

concept helps to explain how simple genetic anomalies give rise to complex aberrant
behavior such as excessive food craving.
The Symbiotic Diet is the culmination of this understanding. Based on 20 clinical studies
to date (with more underway), a natural product was developed and patented to augment
the brain reward cascade and induce a natural release of Dopamine, without adverse side
effects, required to satisfy all craving behaviors.68-74

What do neurotransmitters & Certain

Hormones do?
The first important fact to remember is that many brain chemicals have both stimulatory
and inhibitory effects on eating behavior and metabolism. We will only briefly review the
effects of Norepinephrine, Dopamine, Serotonin, Opioid peptides and Leptin. The major
point here is to educate you as to how these potent brain chemicals directly impact an
individuals romance with food and that improving the role and interactions of these
substances may be important to reducing craving behavior.75

Serotonin76
This well known neurotransmitter is associated with mood, sleep patterns, dreaming, and
visions. It influences many physiological functions, including blood pressure, digestion,
body temperature, and pain sensation. Serotonin also affects the bodys response to the
cycles of day and night called circadian rhythm. Adequate levels of serotonin provide
emotional and social stability, while low levels of serotonin are associated with depression;

anxiety; premenstrual syndrome (PMS); increased sexual drive; carbohydrate cravings;

violent behavior; obsessive thinking; alcohol and drug abuse; and suicide. The following
points depict the role of serotonin (5HT) in eating behavior:
Serotonin suppresses sugar intake.
There is an increase in the Serotonin firing rate when the brain perceives sweet
foods.
In conjunction with other brain chemicals (certain peptides) Serotonin acts as a
satiety substance.
When you block the breakdown of serotonin with certain drugs called selective
serotonin reuptake inhibitors (SSRIs like d-fenfluramine one of the culprits in the
FenPhen saga) you reduce the sweet-tooth (and induce some undesirable
psychological side effects).
SSRIs also enhance metabolism, which could contribute to weight loss observed
with these drugs.
Serotonin blocks the sweet tooth action of Norepinephrine due to stress induction.

NorepinephrinE (NE)77
Generally this is the brains arousal substance and pro-stress molecule. The more excited
an animal becomes the faster NE nerve cells fire. In fact, when there are high
concentrations of this substance in the synapse, eating occurs. Moreover, NE is responsible
for certain food selections. The following points depict the role of NE in eating control and
behavior:
NE increases ones desire for carbohydrates compared to fat and protein.

 NE increases body weight by increasing appetite for carbohydrates.

NE receptor blockers reduce feeding behavior.
While certain brain sites stimulated by NE increase eating other sites actually
decrease eating so it is very complicated.

Dopamine (DA)78
Dopamine is associated with pleasure, motivation, alertness, concentration, and euphoria;
touted as the primary neurotransmitter of reward. It is well known that under stress, we
release a hundred times more dopamine than we do in a normal resting state. Adequate
levels of dopamine allow you to focus, to complete tasks, to feel energized and motivated,
and to experience pleasure. Low levels are associated with depression, lack of
concentration, poor cognition, poor motivation, and difficulty initiating and/or completing
tasks. The following points depict the role of dopamine in eating behavior:
DA suppresses feeding behavior like amphetamines.
DA affect on eating behavior occurs in the reward site of the brain (n. accumbens).
DA contributes to amphetamine induced anorexia.
Blocking DA receptors increase eating behavior causing obesity.
Taste and smell actually release nerve cell DA.
DA released into brain synapses at reward sites stimulates satiety.
DA may block the stimulatory eating actions of the brain peptide GAL, thereby
controlling eating behavior.

 Feeding behavior releases DA into the reward site of the brain. This suggests that
brain DA is involved in learning what, where, and when to eat, more than in the act
of eating.
DA is a positive natural approach when released by food by activating both
Dopamine 1(D1) and 2(D2) receptors (remember there are 5 different dopamine
receptors).
Blocking DA receptors increase sugar intake.
Animals eat more when the DA levels are low.
Low levels of DA lead to high GI foods (i.e. high glucose release) as well as any drug
or food that releases DA.
Reduced DA function (or DA resistance) increases the desire to eat.
Reduced DA function (or DA resistance) causes a blunted response to palatable food,
increasing food intake.

Opioid Peptides79,80
The popular term Endorphins represent ubiquitous natural brain opiate-like compounds.
The word endorphin is a blend (portmanteau) of the two words, endogenous morphine
(endogenous means made within the body). This class of compounds includes at least
three peptides: endorphins, enkephalins, and dynorphins. These are associated with
pleasure, orgasm, euphoria, and pain relief. These compounds are even associated with the
runners high or second wind. Low levels of endorphins are associated with physical and

emotional pain, addiction and risk-taking behavior. The following points depict the role of
opioid peptides in eating behavior:
Opioid peptides like endorphins are reinforcers and are involved in bingeing
behavior.
In the reward site of the brain certain endorphins stop eating.
Certain endorphins bring about an aversion to food in certain parts of the brain.
Depleting or blocking the actions of specific endorphins decreases the desire for
carbohydrates and enhances the desire for fat and protein foodstuff.

Leptin81
In recent years, scientists have been able to discover interesting information about obesity
from working with the obese ob/ob mouse, which inherits earlyonset obesity as a
recessive trait. The ob gene has been cloned and its gene product was identified and given a
name of Leptin. Leptin production can be increased by certain hormones such as insulin
and glucocorticoids. The leptin receptor has also been identified and cloned, and defects in
this receptor lead to ob/ob mice. The role of this protein has been extensively studied. The
following points depict the role of leptin in eating behavior:
Leptin reduces food intake.
Leptin reduces insulin secretion.
Leptin reduces body weight.
Leptin increases energy expenditure

 Leptin normalizes blood glucose.

Fasting markedly reduces circulating leptin.
Leptin cause dopaminergic activation.

The Symbiotic Diet

The Symbiotic Diet is a combination of scientifically researched nutraceuticals directed at
replenishing the gene based neurotransmitter deficiencies of multiple pathways in brain
reward-metabolic targets (DRD2, 5-HTT2a., PPAR-Gamma, MTHFR and Leptin genes,
among others) and diet. The formula works by promoting a healthier brain reward cascade
and will provide fat regulation, cell repair, significant fat loss benefits, overall health and an
improved sense of happiness82 This neurological nutrient amino-acid based composition
[KB220Z Neuroadaptagen-Amino-Acid Therapy [NAAT] will cause the synthesis of the
brain reward neurotransmitters and, through its effect on the natural opioids and by virtue
of inhibiting GABA, cause a significant release of dopamine at the Nucleus accumbens.
When you take the formula as directed, the constant release of therapeutic amounts of
dopamine to occupy the dopamine D2 receptors, possibly over time, effects RNA
transcription leading to a proliferation of D2 receptors, resulting in reduced stress,
increase pleasure in the food they do eat and reduced food craving.83

How was the formula created and Is it based

on research?
Since the passage of the Dietary Supplement Health and Education Act (DSHEA) in 1994, the
nutrition industry has grown dramatically on the back of an explosion in nutrition science driven
by consumer demand, and often sponsored by an ever-growing population of ambitious
marketers trying to achieve commercial success. The cost vs. return-on-investment challenge is
to achieve maximum commercial impact with the best evidence possible for the smallest
research investment. Federal regulators routinely take actions against companies they charge are
misleading the consumer by promoting their products without adequate scientific support. Few
researchers or companies have invested in doing the necessary scientific research to accomplish
the unparalleled level of excellence in the development of the proprietary Symbiotic Diet
formulation.
Excellence in the nutrition industry is the result of diligent sacrificial devotion to bringing the
best products to market. In proportion to the industry, it is research from a relatively small cadre
of devoted scientific icons that creates profound commercial opportunities. LifeGen scientists
have invested in an overwhelming and robust level of scientific research to provide irrefutable
evidence of the unique quality and efficacy of the patented formulation in the Symbiotic Diet.
The present proprietary formulation is the result of over 40 years of research, including 20
clinical studies (so far), by Kenneth Blum, Ph.D. and others. The process of creating the most
efficacious (and patented) formulation was a prolonged and laborious journey. Starting with just
a single ingredient, a dose was tested to determine a baseline effect. Then the dosage was altered,
both up and down, to determine comparative effects. Testing and retesting various doses created

a range of dose-dependent effects until the ideal efficacy was achieved for a single pathway.
Then, a second ingredient went through the same process to determine the optimum effect in
another pathway, after which the two ingredients were combined and tested to determine the
optimum combined effect and dosage. Then a third ingredient was tested to determine an
optimum dose-dependent effect for its intended pathway. Then the three ingredients were
combined and tested again and again. When a formulation was deemed ready, a formal study
was conducted, usually in animals, to confirm the biological effect. This meticulous scientific
process was repeated hundreds of times over the decades for some 40 ingredients (some of which
were ultimately rejected) and ingredient complexes, culminating in the present proprietary
Symbiotic Diet formulation; providing the only known Dopamine D2 receptor activator or
agonist. This unique formulation (US and international patents already issued with other US and
international patents pending), which includes trademarked and branded ingredients, represents
an evolution through literally hundreds of variations of both ingredients and dosages.
Duplicating this formula would require testing up to 240 formula variations (that is 2 to the 40th
powerpotentially over 1 trillion variations) in an impossible trial and error process. This
process would be too costly, arduous, and highly unlikely for any copycat competitors.
Just as important, ingredient selection required establishing and adhering to the highest standards
for ingredient quality and specifications to ensure consistent results. In the real world, ingredient
specifications (actual and purported) vary wildly from low potency and low quality to high
potency and high quality (you can even have low potency high quality ingredients). Most
manufacturers dont disclose qualitative details of their ingredients (and most customers dont
know or dare to ask). In fact, even after a formula of generic commodity ingredients is
completed, it is still a common practice to substitute cheaper ingredients from alternate suppliers.

Keep in mind that almost nobody substitutes with an upgrade in quality and cost; they almost
always downgrade the cost and quality.
Almost all finished product companies use un-refereed ingredients from contract manufacturers
or commodity ingredient suppliers that are selected on the basis of price. A few companies use
evidence-based ingredients (relying on standalone research) purchased from an ingredient
supplier. Almost none (none that we know of) establish quality standards against efficacy criteria
and then qualify already evidence-based premium quality ingredients with their own analytical
panels; using those ingredient formulas in original research, as LifeGen does. In the evolution of
research on the patented formula in the Symbiotic Diet (Synaptose), the use of an ingredient
from different suppliers provided researchers with valuable information about how ingredient
variations altered ingredient effectiveness. Seemingly small changes dramatically diminished the
effectiveness of the product. At LifeGen, ingredient validation and standardization is mandatory.
A rigorous process of ingredient analysis and quality assurance ensured selection and
confirmation of premium quality GMP-adherent ingredients with the most consistent
specifications that achieved the best effects. Select ingredients used in research were coded to
enable accurate evaluation of comparative consistencies and effects. Human studies were
conducted to confirm and validate a variety of therapeutic effects after which select validated
ingredients in the formula were branded and trademarked.
Perfected over decades of research, the patented formula in The Symbiotic Diet and its
variations, based on delivery methods, evolved through literally hundreds of iterations. Validated
by dozens of studies, hundreds of scientific papers and (to date) 20 human studies, LifeGen has
gone to extreme lengths to validate the efficacy and protect the authenticity of this remarkable

technology. Even the slightest variation or alteration in ingredients or potencies has been
scientifically proven to reduce the synergy and effectiveness of the formula. The Symbiotic
Diet boasts a unique and effective formulation that has overwhelmingly exceeded the expectation
of its creators. Synergy, in general, is defined as two or more agents working together to produce
a result not obtainable by any of the agents independently. The Symbiotic Diet is the culmination
of synergistic excellence, symbiotic achievement, and therapeutic efficacy.
The anti-craving effects of this remarkable technology, among many other benefits, have
been observed in numerous peer reviewed published clinical trials including randomized
double-blind placebo controlled studies.84,85 Dr. Nora Volkow, now director of the National
Institute of Drug Abuse (NIDA) and her group at the Brookhaven National Laboratory
found that obese subjects weighing over 300 pounds have reduced numbers of dopamine
D2 receptors in their brain by using a special imaging technique compared to matched thin
subjects. In addition, it has been found that there is a high level of circulating
norepinephrine NE in obese subjects and has been shown to induce feeding behavior in
Zucker mice.87
Recent support on the role of dopaminergic gene polymorphisms (i.e. D2 A1 allele) and
obesity was reported by Stice et al.61-63 In 2008, Stice and colleagues, using functional MRI,
found that subjects may overeat to compensate for a blunted or hypo functioning dorsal
striatum, especially in subjects carrying the dopamine D2 A1 variant (DRD2A1 allele). This
work has been augmented by a recent study showing independent of gene data any blunted
response of the reward Brain site will cause weight gain.
Weight Loss Tips

Nature has its own laws and will never allow violation without revenge.88 A healthy and
intelligent lifestyle that maintains a healthy body composition involves eating a variety of
wholesome fresh foods (not refined carbs and fats), breathing fresh air, drinking pure
water, sufficient sleep and adequate exercise. Having a healthy outlook and healthy
thoughts are also deemed important in promoting optimal physical and mental health.
Food intake and nutrient quotas are constantly evaluated by the body to determine if
additional food/nutrient resources are needed to fund biological functions. As previously
mentioned, all cells, tissues, and organs of the body are genetically programmed for
survival. Inadequate nutrient/calorie resources can result in a protective lowering of the
basal metabolic rate, increases in fat storage, and increases in appetite, all designed to
minimize energy loss and ensure survival.
If you dont use it you lose it!
Exercise is an important component of a healthy lifestyle. However, in an effort to lose as
much weight as possible in the shortest time possible (a dangerous objective!), many
dieters engage in exercise that involves excessive prolonged exertion. We all perceive that
athletes are a super healthy segment of the population and therefore deduce that excessive
exertion must also be beneficial. However, research in elite athletes demonstrates that they
have a high incidence of stress fractures, an increase in unhealthy bone loss, and other
common maladies. 89.90 The best type of exercise for long term healthy and sustainable
reductions in excess fat is a regular routine consisting of a combination of moderate
aerobic (definitely break and sustain a sweat) and weight bearing exercises. This type of
program is what the body was designed for, responds best to, and is body friendly.

Understanding the evolutionary concepts related to eating behavior and genetic

antecedents such as the thrifty gene (inter-relationships of fasting/starvation and fat
production) enabled us to develop these newer concepts about how genes relate to overweight and eating behavior.91
Small Frequent Meals
One important fact in understanding eating behavior is that over-weight individuals eat
fewer meals than normalweight people. Interestingly, in 379 men, aged 60-64, those who
ate one or two meals per day were heavier, had thicker skin, had higher levels of
cholesterol, and frequently had impaired glucose tolerance as compared to men who ate
three or more meals per day. Others studies support the fact that frequency of eating also
changes the metabolism of glucose and concentrations of cholesterol and it is well
established that glucose (in junk food) is an addicting substance like alcohol, opiates and
cocaine.92-105
Glycemic Index (GI)
To help us determine how quickly a specific food can turn into glucose, there is a measure
called the Glycemic Index (GI). In fact, the higher the GI the quicker the food will release
glucose into the blood stream. Yes! We want to eat slow-release carbohydrates, which will
bring about more stable blood sugar levels. Such foods with a low GI include unrefined
grains, and certain fruits like apples and pears, but not raisins and/or bananas. Moreover,
all vegetables are slow releasing. The point here is that one way to maintain a healthy
weight would be to eat low GI foods and combine these foods with protein. However, in
attempting to understand craving behavior especially for sugar, we must understand that

those individuals who are prone to addictive behavior, including sugar bingeing, may have
a genetic predisposition for consuming high GI foods to obtain the high induced by
releasing sugar into the brain resulting in dopamine release. This simply is another way to
avoid the blues. In fact, it has been speculated that sugar may promote the blues.
Overindulgence in high GI foods causes a spike in dopamine release. This results in a
depletion of stored nerve cell dopamine; and this lack leads to depression. It is now known
that certain gene variants induce a higher likelihood that a person would select various
types of nutrients sugar vs. fat vs. protein.106 The dopamine D2 receptor (DRD2) has been
implicated in modulating the rewarding effects of foods high in sugar. Recently Eny et al.106
determined whether a variation in the DRD2 gene affects habitual consumption of sugars in
a free-living population. They found that carriers of gene variants in the DRD2 gene select
sugar over both protein and fat. This finding takes on real importance when we consider a
dietary program. Compared with women who consumed a conventional healthy diet, more
women who consumed a low-GI diet showed improved menstrual cyclicity and well-being.

conclusion
Weight loss, weight gain and weight management are the most common terms used to
express changes in body composition, particularly regarding fat mass. However, focusing
on weight as an accurate measuring criteria poses a contradiction to the natural sequence
of processes in recompositional metabolism, creates inappropriate expectations, and does
not provide a correct and accurate perspective for evaluating healthy changes in body
composition, as fat is the lightest of pertinent macro molecules.

More importantly, fat is usually the last to go in the body recomposition process, therefore,
creating short-term expectations is erroneous. In fact, rapid weight loss imposes and
simulates a famine on the body, demanding a protective energy-saving reaction. Fat
metabolism is influenced by many factors from genetics to lifestyle and the efficiency of
energy metabolism. Existing weight loss tactics for the most part have failed to provide
successful means to achieve sustainable healthy body composition and improve healthy fat
loss. Commercialized weight loss programs, even medically supervised versions, do not
consider the bi-phasic nature of genetically regulated set point defense response
mechanisms that mandate preservation of body fat stores against famine and survival
threats simulated by aggressive weight loss tactics during phase 1.
Further, existing tactics place an erroneous emphasis on caloric intake to the exclusion of
considering nutrient quality and density of those calories, a factor far more important to
metabolic competence than calories alone. As an analogy, evaluating the quality of a diet by
the quantity of calories is like evaluating the quality of art by the size of the frame. This
overview provides support for a novel body recomposition and healthy body mass
management technology. A unique evidence-based formula coupled with a low refined
carbohydrate diet and method to safely and naturally induce effective body recomposition
and achieve healthy body mass management objectives is presented. This novel technology
contrasts with existing tactics to manipulate body composition in that it is based on the fact
that sufficient nutrition (as opposed to just calories) is required to fund a wide range of
factors involved in achieving healthy and efficient metabolic function. This technology
combines a patented composition of synergistic nutraceutical ingredients (KB220Z
neuroadaptogen technology) necessary to simultaneously address symbiotic mechanisms

that promote healthy metabolism in the energy management system, stress and
inflammation management system, the pleasure/food craving management system
(controlled by the brain), the immune management system and the neuroendocrine
system. Importantly, these five systems are homeostatic, intimately interactive, and
interdependent in ensuring optimal metabolic function.
This novel nutraceutical technology optimizes genetically programmed energy expenditure
and storage functions, without inducing Yo-Yo rebound weight gain consequences. In
contrast to conventional short term expectations, weight loss might not be expected since
the need to improve the health of the cellular energy producing apparatus might first result
in increased muscle density and weight gain that is needed to promote healthy and
permissible fat oxidation and loss. In fact, a more normal and expectable sequence of
events in the corrective healing process might include initial water weight loss, increased
muscle density and weight (muscle is heavier than fat and water) followed by permissible
fat loss, which could take some months to achieve. Such a sequence could and has
contributed to disappointment with short term weight loss results and abandonment of
healthier more intelligent programs that would lead to sustainable and greater fat loss in
the healthy body recomposition dynamic. The novel KB220Z neuroadaptogen technology
works best for those that need it most; and works better with time.
The well established understanding that food cravings may not be dissimilar to any
psychoactive abusable drug in terms of neurochemical and neurogenetic mechanisms is the
cornerstone of the novel Symbiotic Diet. Indeed, correcting the hypodopaminergic brain

state will reduce abnormal craving behavior (hunger pains)108 especially sugar bingeing
and provide a real potential of becoming thin109 and healthy while feeling good.

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