Based on Avant Labs’ groundbreaking original formulation, LeptiGen II is
designed to deceive one’s body into thinking it is being fed without necessitating
the calories traditionally required to elicit the hormonal response typified
by the fed state. The dieter can now bypass the detrimental effects of the
starvation response—metabolic downregulation and plateaus in fat loss, increased
loss of Lean Body Mass, surge in appetite, fatigue, etc.—without the implementation
of frequent, and often progress-hindering, refeeds. While other supplements
offer only to camouflage the secondary effects of dieting, LeptiGen II prevents
the actual genesis of these obstacles through the manipulation of their hormonal
source, before they can become a hindrance to the realization of one’s goals.
Introduction
LeptiGen - Prototype 2 represents far more than a shift in trends in the
bodybuilding and performance supplementation realm. What it represents is
a fundamental shift in the way one understands and conceptualizes the human
body (and basically all biological processes). Basically, I am proposing
a new, comprehensive, and unified paradigm concerning all things biological
:)
It encompasses and integrates research and theory from numerous disciplines
and sub-disciplines -- everything from exercise science to biochemistry to
evolutionary biology to molecular biology to philosophy to Holistics to "old-school",
to things generally thought best left to hippies -- and, the full gamut from
basic in vitro research to anecdotal reports on message boards.
But, before you can understand and appreciate the breakthrough that LeptiGen
p2 represents, you will first need to be introduced to, and indoctrinated
in, the new Gospel of Par Deus.
It is the paradigm from which LeptiGen p2's design, as well as the design
of our products in the foreseeable future, takes form.
It is a synthesis of the two equally short-sighted and misguided perspectives
prevailing in the literature, and reflected in our little world, on several
different levels. We have elucidated and shall unveil, about 10 theorems,
that, on their own, would generally be major breakthroughs, in our world,
but we have unified it all under a single, beautiful paradigm, which WILL
be a breakthrough, in the literature, when they figure it out, in 5 years.
As with all things that push the boundaries, large amounts of direct evidence
is lacking in certain areas of our research (or it wouldn't exactly be revolutionary).
As you will see, there is, however, a truly prodigious amount of indirect
evidence, which, when analyzed as a whole, with the help of our friends logic,
critical analysis and creative genius, is both loud and eloquent in its support
of our argument.
Editors Note: Before we move further, I cannot emphasize enough
the importance of the whole for understanding the parts and vice-versa. And,
I mean this well beyond distinctions of in vitro vs. in vivo. As this is
best viewed as a collected body of work, it will be presented as such --
it will be organized into major points, with the data in support presented
as a semi-organized whole because it defies typical uni-directional linear
representation because the body does signal either linearly or uni-directionally.
The relatively abbreviated nature of "teaser", reinforces this set-up. I
have tried to stick to the theory in the text, with examples here and there,
as opposed to detailing a study every other line (that write-up is in the
works) -- instead, I have just placed references at the end of the write-up,
summarizing the significance of each one, and divided them into groups, based
on the aspect of the paradigm they provide support for.
So, with that aside:
Survival, Reward, and You
The essence of biological systems is survival and propagation, basically
by definition. Billions of years of evolution created us and genetic coding
that sent reward signals for anti-life behavior would result in extinction,
and has thusly been generally eliminated at the genetic/instinctual level.
So, everything we do, scientifically, will be with survival advantage for
the organism omnipresent in the back of our minds (alas, there will be no
Creationist themed Avant Labs products in the near future).
We humans should add "happiness" to that, as should we bodybuilder (yes,
it has positive repartitioning effects), because it is signaled by the same
reward pathways. So, let us look at the nature of our survival, propagation,
and happiness in greater detail.
The War Machine
There is exactly one good reason to be “one with nature” – to dominate it.
Life is essentially a war of all against all -- even within one’s own body
(bacteria, viruses and cancer, are such examples of warring agents). Natural
selection IS war, survival, and propagation -- from the first atoms that
found it "beneficial" to form a molecule, then a cell, and so on, to the
current penultimate organism, Rational Man and his Empire.
At the macro level, it is obvious – “Mother” Nature sends us pestilence and
famine and natural resources galore, we counter with the insertion of our
intellect into matters. We are occasionally more civilized when warring with
each other, but most still prefer versions of force over the thought and
reason, and considering that is all life had to work with for the first 99.99999%
of evolution, it should not surprise that a lot of this is still wired into
our genetic code.
Not so obvious, is what goes on at the micro level, between body and environment.
Examining the nature of the skin barrier, Phase I and II acute “xenobiotic”
responses (everything is a “xenobiotic”, as with war, we keep the spoils,
destroy and discard the rest), inflammatory cytokines, local expression,
leaves one with the impression they are housing World War III, 24-7.
We would do very well conceptualize biological systems as such in our mind’s
eye, and we would do very well to treat the matter as such, in our attack.
One does not just send a single plane with a nuke in, except when it is time
to fuck something up proper. Our goal is supraphysiological health, aesthetics,
and performance, which requires a bit more strategery than that. Instead,
we should attack the problem from multiple fronts and with multiple tactics,
like an army -- and like the human body (“community effect” and “entourage
effect” are two terms in used the literature).
The Homeostatic Imperative
What our means of defense aims to do, ultimately, is produce homeostasis
(make a note, ‘tis Way Important ™ ) -- we adapt to weight training, because
it is an attack on the status quo at numerous levels -- electrical, mechanical,
chemical, etc., which cells perceive as “uncool”. So, they produce pain so
you won’t do it again tomorrow (and probably does some long-term coding in
the brain as well), and then supercompensates, because billions of years
of evolution has shown that we’ll not only do it again, but that it is beneficial
for survival and propagation (and that some us will even schedule our life
around purposely doing it, day after day).
Let us call this the Homeostatic Imperative.
Interestingly, one the way body does so, in regard to weight training, is
to make the muscle fiber resistant to the cellular stress response evoked
from training, but that is a topic for another day.
If There Were a Magic Bullet…
I can think of exactly two places where your magic bullet properly belongs,
and neither of them are a scientific discourse on the betterment of a biological
system.
The body is profoundly redundant in its setup and operation. Basically, we
just evolved one system on top of another, as it proved useful for survival.
The previous system, however, did not just disappear, as if the higher system
or organism were created anew by magic. Instead, it stuck around and just
helped with the same job. That extreme redundancy might be most beneficial
for survival, in case the foodstuffs containing essential micronutrients
become unavailable during the days before science and supermarkets, does
not take a fantastic leap of logic.
And, in combination with the homeostatic imperative, it does not take a great
leap of logic to suggest that the Magic Bullet and the related Godfather
Hormone approach is inherently retarded, on multiple levels (yeah, I know
I greatly helped propagate the latter in my Leptin articles and postings).
Unfortunately, this is the dominate medical approach, and, as such, it is
the current dominate academic paradigm.
How the idea that simple, massive, overconsumption of a nutrient might not
be the best approach for manipulating a system whose nature is specifically
to prevent massive overstimulation of ANY signaling pathway has not occurred
en masse – be it due to conspiracy or myopia or lack of talent or whatever
– I am not sure. I mostly know it’s retarded. Mostly.
Yin-Yang in this Thang
Such, is just not how the body chooses to do business. It does so via the
manipulation of countless LOCAL signals, modestly elevated or reduced, working
in unison. Under such conditions, quite a bit of evidence exists that, contrary
to the wrath of protective feedback inhibition, when proper substrate is
available in PHYSIOLOGICAL amounts, a positive feedback cycle is produced.
We witness this phenomenon with the inflammation/anabolic response to exercise,
with sex hormone action (and I think pulsatile release is an artifact of
this phenomenon, but I lack sufficient evidence), with tumors, prostate hypertrophy,
hair-loss, body-hair growth, or in any situation when there occurs a loss
of control of substrate imbalances.
The body is quite good at preventing this (truly, profoundly, remarkably
so, in fact), but it is not perfect – chronically place excessive pressure
on any system, and it will eventually fail.
So quit abusing it.
I am not directing this comment at the slothful and gluttonous -- I am speaking
about We of the Bodybuilding and Human Performance persuasion. Let us cease
looking for the magic pill and the magic routine, and start looking at how
genotype met environment to produce the phenotype you see looking at you
in the mirror, how it does so in others, and why.
Chances are 100% that you are doing a bunch of stuff right (what "works for
you"), but without having a clue as to why, while also doing a bunch of stuff
wrong (which works for lots of others), because without the “why” and “how”
, you cannot take context into account -- and, context is EVERYTHING
to the cell.
Environmental encounters will have dramatically different effects depending
on the existing biochemistry (be it mostly genetic in origin, or otherwise).
It thus follows, that without a true understanding of wherefores, whatnots,
and how-so's, one is going to draw false conclusions from study after study,
and experience after experience. If the core determiner of biochemical reaction
is not understood, its subsequent manifestations cannot be either.
You have hopefully noticed that the same environment will not only produce
very different results in say the DoWA mesomorph vs. the "hardgainer" ectomorph
, so too will it produce different results in you, given your current biochemical
profile (on 1g of test per week, for example, vs. “clean”, or even at high
body fat vs. 10 weeks into your diet.
IOW, the Chicken Without a Head Approach to Diet and Exercise ™ almost certainly
leaves you greatly lacking in efficiency and results.
Phenotype = Genetics + Environment
Everything the body does, it does for a reason. Namely, perceived survival
benefit. If fatty acid oxidation and protein synthesis decreases, and your
sex drive goes away, it is because your cells are getting signals that your
body is starving and not getting signals of the opposite nature.
The last thing you would need, is the inefficient, DOMINATE phenotype and
another mouth for the village to feed, because right now, nutrient signaling
pathways are indicating that life is kicking your ass.
Furthermore, it does its bidding through specific pathways -- though prodigious
in complexity, it is not random. Transduction, translation, and transformation
are the result of specific FOOD DERIVED NUTRIENT SIGNALS – everything else
just influences those.
Change the signals, you change the phenotype. Good genetics are most welcome,
but clearly, we can influence the phenotype, for good and for bad, by changing
our lifestyle. The pathways and signals responsible for production of the
phenotype are rapidly being uncovered , so one would do very well to take
them into consideration. Look at why what works does in fact work. Meaning,
analyze the signaling mechanisms involved, and manipulate them as efficiently
as possible through properly designed exercise, diet, and supplementation
for your situation.
You could save several years by letting us do most of the legwork for you,
which is what we have done with LeptiGen -- and what we will do beyond. Though,
methinks it a fairly magnificent beginning, LeptiGen Prototype II truly is
but the beginning of what we are going to do in the near future.
Mmmmm…… Cocoa Pebbles
Before rational man, the organism needed a very strong signal to let it know
what it needed to do for proper living, particularly in times of scarcity.
Things have strong tastes for a reason. Unfortunately, one’s goals and needs
are generally not in harmony with one’s genetic tendencies, nowadays, so
the issue is far more complicated than “yummy = good for you” (ancestors)
and vice-versa. This situation has literally caused an epidemic in times
of plenty, as the genetic coding that calorie dense foods are precious and
wonderful is still very much existent and active, but it now takes essentially
zero effort (physical and otherwise) to attain this nourishment.
Don’t fret, it gets much worse :) -- many have come to possess a "thrifty"
genotype. Unfortunately for these individuals, large amounts of muscle and
high rates of FFA oxidation and lack of need/desire to eat are the thrifty
genotype’s antithesis, so the nutrient partitioning situation can get ugly.
Compare this, for example, to the West African, badass genotype (gorillas,
rhinos, lions, elephants, pro-athletes), which evolved with continuous abundance.
Fortunately, these same signals also open up quite a few avenues of attack.
The body has a fair number of reward signals that indicate living right,
as well as a vast number of pathways that mediate these reward signals (and,
which these reward signals conversely mediate -- did I mention that EVERYTHING
is connected). This same reciprocal, intertwined signaling extends to the
process of telling the organism to stop a behavior that is anti-life as well.
Dopamine, opiates, GABA, NE, Cannabinoids, PEA, NMDA and more are part of
this reward signal, but, again, balance is key. Get something too high or
run out of a needed substrate, and the organism shuts down those processes
to avoid damage. And because these bodily functions are all interrelated,
this shutdown of one process will often take the good stuff with it (like
protein synthesis or nutrient uptake).
There is far too much info to get 100% precise on our approach without a
computer algorithm of some sort (Spook and I have that on the agenda – mostly
him). Worrying that we do not know every pathway in its entirety is akin
to fretting over atomic physics in regard to its application in hitting a
baseball.
If we take the big and small picture into account — in vitro and in vivo
-- the macro and the micro— the forest and the trees –- real world and the
lab -- we can clearly see pattern after pattern, and pathway after pathway,
many screaming to be rationally manipulated for nutrient repartitioning.
So, if we are vigilant in cultivating an awareness of these patterns, we
can carefully manipulate them via little pushed and pulls in the proper directions
and do infinitely better than the 2/3 blind approach that is currently being
employed.
This, of course, begs the question: what are these so-called “patterns”,
of which you speak? And, of course, what are the proper directions in which
we need to push them in order to attain the DOMINATE phenotype?
Phenomorphosis: The Fed State
Well, this is for LeptiGen, so let us start there. As you recall, the point
of LeptiGen is to trick the body into thinking it is being fed when it is
not. We have discussed the fed state in regard to metabolic parameters of
an organism, in our “Leptin” series. Namely, the fed state is conducive to
fast, muscular, and “metabolically inefficient” phenotypes, with the vice-versa
also holding just as true, if not more.
However, this phenomenon is actually signaled at the cell level, and the
fed cell is a metabolically active cell, in regard to overall metabolism,
fatty acid oxidation, protein synthesis, and much more.
Obesity does not occur in the wild (animals eat what they need, then get
a signal to stop). But, keep Rover and Kitty’s bowls full, with delicious
vittles, and it is a different story. Obviously, that communication between
nutrient signaling and calories and reward is proper fucked in an even larger
percentage of human people.
But, what does that have to do with We, the Lean??
Everything.
We too, are very oft not getting the proper "fed" signal, though, our is
a result of self-imposed starvation, to a great extent (as far as calories)
– again, read my leptin articles if unaware of the negative partitioning
invoked by the starvation response.
What we are not aware of, is that calories are almost meaningless, per se
-- it is the strength of the signal sent at the protein level and in what
tissues it is signaled that determines the phenotype. It is indeed foodstuffs
and their metabolic byproducts (along with other aspects of environment,
which we will not get into too much (sunlight, oxygen, pathogens) that determine
this signaling, so adjusting caloric intake will affect all of this to some
extent, but it is not going to be remotely linearly correlated (unless you
have the perfect diet -- which you don't), because quality is what is of
absolute, prime importance.
Which gets us to our paradigm (in relation to our products, at least) --
namely -- via supplementation, we intend to invoke the fed state by providing
the body with those metabolic byproducts that signal it, but which contribute
fewer calories per unit fed signal then glucose.
Thus, the body will continue FFA oxidation and protein synthesis at high
rates, but instead of having the excess calories, which you previously needed
to reach this state, spill over into adipose, we will get the signal at a
calorie deficit or near maintenance, instead of with massive over feeding,
so the body will draw on existing fat stores to provide substrate/ATP for
these processes, giving long-term repartitioning.
We also intend to push substrate flow to the proper tissues, via manipulation
of pathways that favor muscle over fat.
Food and Mood
We talked about reward signals, quite a bit, in regard to the fed state,
so I will just add that they are quite similar in nature, sharing neurochemicals
and huge chunks of signaling pathways. This goes for responses to sex, to
food, to drugs, and even great ideas.
For example, food-restriction increases the subjective reward response to
both food and drugs. It also increases both dopamine and opiate activity.
This makes sense, on the micro and macro level. First, food restrictions
mimics food scarcity/starvation, so your reward signals would be low, so
the receptors would upregulate simply due to diminished ligand binding. Secondly,
the leptin receptor is found all over neurons for pleasure chemicals in the
areas of the CNS that modulated food related behavior and, not surprisingly,
leptin decreases the reward response to both food and drugs. Fed signals
are then sent in 1000 directions and you are chemically satiated.
There are a number of pathways where the reward and fed response is imbalanced
in the obese, and conveniently, they can be connected to leptin or dopamine
with 1-2 steps. This includes opiate pathways, inositol pathways, and more.
Global Protein Synthesis
Protein synthesis is, essentially, a whole body process, though it is split
up into converging and diverging pathways that make it seem more confusing.
And, contrary to common misperception, significant portions of this signaling
process are essentially immediate – so-called “fast transduction”.
The Mind signals the body, taste buds signal the body, the stomach signals
the body, the liver signals the body, and so on –- and, of course, vice-versa……
and it is all at the cell level….. and it runs the gamut of tissues. All
is interconnected (as you'll see), so anabolic conditions in one cell/tissue
will push the entire body in that same direction (glucose and fatty acids
in insulin resistance is one such obvious example).
This situation of global protein synthesis/anabolism applies to leptin and
other peptide signals and structures like IGF-1, GH, insulin, etc, and likely
to receptor expression as well (until negative feedback hits). IOW, it is
far from confined to the kind that you flex, which is what we normally tend
to think of too often.
The Anabolic Response
The anabolic/fed/protein synthetic response is basically the same for every
component in the body: muscle, fat, the immune system, neurons, tumors, etc.
In all of these systems, the pathways and cycles that determine the anabolic
response (and are reflexively determined by it), including inflammation/cytokine/prostaglandins,
mTor, ion transport, cell-swelling, 2nd messengers, and even mood chemicals,
are virtually identical. These fundamental similarities in process transcend
tissue/cell-type and they transcend species, from the most complex to some
of the most simple.
As mentioned, previously, it is a positive feedback cascade, of nutrients/signals
triggering their own release and the release of others that signal them,
all the while creating more and more potent signals, branching out in a criss-crossing
web, upregulating mRNA billions of times at a billion different points, until
reaching the point where the fact that it is coupled tightly with the negative
feedback side we are more familiar with, becomes apparent (only at the protein
level much of the time, though most of us are familiar with pain, nausea,
cyclic testicular shrinkage, etc. – all of which are negative feedback signals
of one variety or another).
Yin-Yang Back in this Thang
Problems arise, in regard to health, body composition, mood, etc., when concentrations/signaling
becomes unbalanced and askew. Basically, pretty much every bodily process
has an “inverted U” concentration-response curve associated with it, which
is made particularly manifest when essential co-substrates are lacking.
Proper balance is the key to overcoming the limitations of homeostasis. It
should occur that nutrients might compete for absorption and uptake for a
good reason. The body deals successfully with unfathomable amount our nonsense.
Get things semi-right and transform the body is previously unimaginable ways
via foodstuffs and exercise.
Nutrient Hierarchy
On the macro level, we note that the body has a hierarchy for nutrient distribution
– and, again, in evolutionary terms, it makes perfect sense. It is more important
for survival to provide nutrient to brain, muscle, organs, etc., than it
is to provide it to fat tissue. This has profound and wonderful applications
for Rational Man -- namely, uptake mechanisms are going to be more sensitive
in these tissues, and adipose tissue will mostly get the spill over.
The literature on a number of systems backs this up as well, in cellular
and whole-body nutritional states between obese and starving, the hormonal
milieu activates catabolism of fat tissue in order to provide substrate for
increased protein synthesis (PGF2a, testosterone) or to spare glycogen and
muscle protein (AMPK, beta3, PPAR-alpha) at the expense of fatty acids.
Nutrient Repartitioning
Nutrient repartitioning is the key to rapid, long-term body composition manipulations.
Obviously, maintain the fed state, proper, as mentioned -- balanced, full
signaling at all pathways as ideal. The nutrient partitioning improvement
lies primarily in the avoidance of the starvation response from suppressed
signaling, as opposed to the achievement of supraphysiological levels.
And, as mentioned, strive to achieve this metabolic state without a calorie
excess or even in a deficit, via manipulations in nutrient signaling pathways,
using substances that send a stronger signal per calorie than glucose (or
if you want to get fat, do the opposite), for the induction of long-term,
steady repartioning
Finally, make a point to really focus in on the pathways/mechanism by which
one can preferentially stimulate the anabolic response in muscle vs. fat.
Exercise is the most obvious, since it is far easier to activate mechanoreceptors
and induce ion flow (and the anabolic cascade that follows) in contracting
muscle than in fat.
The rest is the essence of LeptiGen p2, and many products to follow.
Local Government
We have implied as much throughout, from start until present, but plasma
levels of a nutrient or hormone in question are essentially meaningless (vasculature
being a notable exception). The full machinery for synthesis and metabolism
of essentially all of the important signals in the body exist locally. This
applies not only at the tissue level but ultimately at the cellular and subcellular/protein
level .
Local is EVERYTHING
Eggs and Omelets
Catabolism, oxidation, and the like, are all part of the anabolic trigger.
It stimulates ion transport, nutrient uptake, cell-swelling -- any of this
sounding familiar…..? :) The key to harnessing the positive attributes
activated by these processes lies, as always, in the attainment of balance
through proper feeding (and filling) of the cell.
Many substances, such as NO, Vitamin C, and NAC can be both anti-oxidant
and pro-oxidant, depending upon context. In addition, most of the signals
we discussed in the “Anabolic response” segment, can be anabolic or profoundly
catabolic, depending on context.
Ideally, one wants to obtain as much anabolic stimuli per unit of fiber damage,
neurotransmitter depletion, high energy phosphate depletion, etc. (thus inroad
to recovery) as possible. At a certain level, anabolism and uptake reaches
a threshold, the muscle cell can’t expand anymore, ions are done being rapidly
transported in and out of the cell, osmoltyes turn off their pager, and protein
synthesis establishes a status quo for the time being.
Anything beyond that ceiling is overkill, as the extended anabolism of a
“sore for a week” workout will not provide an Area Under Curve of anabolism
to compensate for the catabolic hole you dug yourself.
The superiority of more numerous, less destructive workouts seems almost
a given when one considers the homeostatic imperative.
Conclusion (by Tkardde)
So where does this new knowledge leave us so far as real-world implementations?
Let’s recap:
Nutrient partitioning is the key to body composition manipulations. To capitalize,
it is imperative that one:
- Maintain the fed state, as mentioned, via the achievement of proper
balance—full signaling at all pathways. Improvements in nutrient partitioning
lie primarily in the avoidance of the starvation response induced by low
signaling levels, yet does not require the purposeful cultivation of supraphysiological/high
levels, which can in fact be contraindicative to said goals.
- Direct particular emphasis on the pathways and mechanisms by which
one can preferentially elicit the anabolic response in muscle, as opposed
to fat. Exercise is the most obvious method to achieving this end, due largely
to the fact that it is far easier to activate mechanoreceptors and induce
ion flow—and the anabolic cascade that follows—in contracting muscle than
in fat.
- Achieve this metabolic state of equilibrium without resorting to a
calorie surplus. This can be achieved via manipulations in nutrient signaling
pathways by means of the judicious use of substances that dispatch a stronger
signal per calorie than glucose. Enter LeptiGen PII, which has been designed
to do precisely this. Due to its revolutionary effects on nutrient signaling,
the body will continue Free Fatty Acid oxidation and protein synthesis at
high rates, but without necessitating the excess calories normally requisite
to achieving this state.
- As the fed signal will be sent at a calorie deficit or near maintenance
intake, substrate spillover into adipose stores is not only circumvented,
the body will actually draw on existing fat stores to provide substrate/ATP
for these processes, imparting the manifestation of long-term repartitining.
Fat loss will be accelerated, and muscle gained.
This is what LeptiGen does.
Thus, the dieter can now bypass the detrimental effects of the starvation
response—metabolic downregulation and a plateau in fat loss, increased loss
of Lean Body Mass, surges in appetite, fatigue, etc.—without the implementation
of frequent, and often progress-hindering, refeeds. While other supplements
offer only to camouflage the secondary effects of dieting, LeptiGen PII prevents
the actual genesis of these obstacles through the manipulation of their hormonal
source, before they can become a hindrance to the realization of one’s goals.
