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    Recent Entries

    Shock Therapy™
    Microbiotic Rebirth™

    There are trillions of bacteria, living and breeding inside your body, right now. You need some of them to survive, but many of them hate you. For most people, due to genetics and/or diet, the evil ones have gotten the upper hand, attacking you with not only fat gain, but whole body inflammation accompanied by damage to insulin sensitivity, cardiovascular and digestive health, the immune system, and even your skin and brain. Shock Treatment™ combines 5 potent, natural antibiotics to seek out and destroy them, freeing the kingdom of your gut to be repopulated with loyal, benevolent bacterial citizens.


    Currently, probiotics are mostly thought of and used in relation to a healthy digestive system (reducing upset stomach, gas and bloating, diarrhea, and IBS type symptoms) and the immune system (coughs, colds, and general sinus and respiratory health). While they certainly are indeed useful for such applications, the ramifications of an unhealthy gut and microbiota go far, far beyond that.

    The gut and its microbiome are essentially a massive endocrine organ, controlling and influencing basically your entire body and brain. And, given that all of the trillions of bacteria that call it home originally came from outside your body – and entered without your permission – it is by far the most important organ in which we can take steps to manipulate and take back control.

    We will first look at some basic science and data on how this all works. Then, we will look at studies that have shown alterations in the microbiotic make-up of the gut, and the correlations they display in health and disease, suboptimal and optimal fitness, and just general things that everyone would consider part of good or bad life outcomes.

    It is a massive subject, far too much to discuss in complete depth, here, so we’ll do our best to keep it as short and sweet as possible while still giving you enough background in this field to understand the shocking reality, scope, and importance of this microscopic invasion.

    Subsequently, we will get down to business and specifically get into the science of Shock Treatment™, the first step in the process of making yourself king or queen of your own castle, again. We’ll show you how it can immediately ameliorate symptoms, while preparing the gut for a permanent fix, with special emphasis on a lean, healthy body.

    Deus Vult!

    The Basics

    It basically works like this. The Western lifestyle, including diet, lack of exercise, and alcohol use (and, in all likelihood, genetics, though the data just isn’t there, yet) leads to an imbalance of the bacterial composition of the gut (1,2). This results in the excess production and release of inflammatory signals, such as Lipopolysaccharide, TNF-alpha, interleukins, and prostaglandins, which subsequently escape the gut and enter the rest of your body (3).

    Though, they all contribute to the pathologies we will cover in various ways, it is Lipopolysaccharide (LPS) that we will focus on the most. Within the gut, this leads to the general digestive issues and inflammatory bowel syndromes like IBS and colitis that you have commonly known probiotics as being used to alleviate (4).

    While fixing digestive disorders will come along for the ride, our primary focus is going to be on body composition and metabolic health. In other words, we want to make you leaner, protect against diabetes, and help keep you from having a heart attack or stroke. However, there really is so much more to it than that, as a few quotes from the literature aptly demonstrate:

    “Changes in the composition of the gut microbiota (dysbiosis) may be associated with several clinical conditions, including obesity and metabolic diseases, autoimmune diseases and allergy, acute and chronic intestinal inflammation, irritable bowel syndrome (IBS)…” (5)

    “In this milieu… disturbance of the gut microbiota balance and the intestinal barrier permeability is a potential triggering factor for systemic inflammation in the onset and progression of obesity, type 2 diabetes and metabolic syndrome.” (6)

    “Through these varied mechanisms, gut microbes shape the architecture of sleep and stress reactivity of the hypothalamic-pituitary-adrenal axis. They influence memory, mood, and cognition and are clinically and therapeutically relevant to a range of disorders, including alcoholism, chronic fatigue syndrome, fibromyalgia, and restless legs syndrome… Nutritional tools for altering the gut microbiome therapeutically include changes in diet, probiotics, and prebiotics.” (7)

    As you can see, alterations in the microbiota can affect basically everything, but that there is also hope for change.

    Getting back to the gut and body composition, the aforementioned Lipopolysaccharide (LPS) leads to overactivation of cannabinoid receptor 1 (CB1) within the gut, which causes an increase in intestinal motility (speed of food going through) in the proximal parts of the intestine. This leads to less absorption of nutrient feedback signals that tell the brain you are well fed, and that it is time to stop eating (8). Concurrent with this is an increase in transit time in the colon, which results in a greater total harvest of caloric energy from your food (9, 10).

    In other words, the signal your brain is getting is that you are not getting enough food, while you are actually extracting more calories from what you eat. This not only directly leads to more fat accumulation from harvesting more calories, it lends itself to over-eating. This aggravates the cycle further, as overeating and increased adiposity are themselves inflammatory. So, what you have is more inflammation, more dysfunction, greater food intake, greater extraction of food, more fat accumulation, then REPEAT!

    The carnage does not even end here. Along with this inflammatory state is a disruption in the intestinal barrier. Intestinal permeability is increased and these inflammatory agents spill out systemically. This is often called a “leaky gut”. This results in a low-level inflammatory state in the entire body. The biggest culprit here is, once again, LPS (11).

    LPS activates CB1 receptors in the body and brain, just as in the intestine. In the fat tissue, this leads to activation of PPAR-gamma, and an upregulation of triglyceride synthesis, fat cell formation, and fat storage (12). In the brain, activation of CB1 increases orexegenic pathways, thus increasing appetite, hunger, and ultimately, food intake (13). This should not much as much of a surprise considering “the munchies” that accompany intake of famous cannabinoid receptor agonist, marijuana.

    And, LPS is not done yet, not at all. It also activates Toll-like Receptor 4 which, along with other inflammatory signals (TNF-alpha, interleukins), promotes both insulin and leptin insensitivity, peripherally and centrally (14, 15). At this point, your adipostat (the thermostat for your body fat level) is wrecked. Your ability to control food intake is gone, and you are a fat storing machine. Obviously, this is not what you want your body doing to itself. It is not what you want it doing to you. It is not what you want it doing to your life.

    Oh, and to top it off, atherosclerosis, heart disease, and stroke are promoted by these same inflammatory pathways. Combined with the increased body fat and insulin resistance, you officially have all of the perfect ingredients for the dreaded Metabolic Syndrome (16, 17).

    And, it is just a bunch of microscopic bacteria that call your gut “home” causing all of this devastation.


    See "References" here http://neobium.org/product-line/shock-therapy/#1 for references.

  1. Leptin and shit

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    Recent Entries

    LeptiGen ushers in new paradigm in science and supplementation



    Par Deus


    Avant Research



    O happy day!


    LeptiGen - Prototype 2 has finally pulled into the gate, after much anticipation and much delay.


    You, our dearest customers, will obviously be the final arbiter as to whether it was worth the wait, but we are certainly feeling pretty good about our formula and ourselves J




    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 J


    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, their 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 quite 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 J -- 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?





    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??




    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…..? J 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.










    aka “A summary for the lazy or dim”

    by Tkardde

    ---- to be added ----










    The Data



    Everything connected, everything in its place:


    10386770 -- mechanotransduction (multiple cell types), local IGF-1


    12490597 -- oxytocin, PGF2a, and Ca2+ transport


    11976264 – Arachidonic Acid metabolites and penile dilation


    12005362 -- DA receptor may have evolved from ATP/GTP receptors.

    9560443 -- IGF-1, Ca+/calmodulin, alpha1, and K+ channels


    12169444 -- leucine activates protein synthesis in all cell types tested


    9227529 – Acetyl Choline stimulates release of NO and PG, causing vasodilation


    2481442 -- NSAID blocks insulin stimulated mRNA synthesis


    9044432 -- hypoxia, Arachidonic Acid, PGF2a, and glucose uptake



    8468370 -- mechanical stimulation and 2nd messenger release in muscle (IP3 and DAG)


    8141783 -- alkalosis and ATP increase IP3 and DAG


    43142 -- hydrolysis of Arachidonic Acid from PhophatidylColine increased by histamine and retinoic acid, as well as PGE2 and PGF2a


    12225698 – Acetyl-l-carnitine (ALC) increase dopamine (DA) and serotonin (5-HT)


    8364354 -- ALC potentiates NE and DA increase in adenylate cyclase activity


    8474576 -- ALC as stimulator of amino acid osmolytes


    12580938 -- correlation between leptin and total body water


    12565709 -- leucine promotes glucose uptake in skeletal muscle
























    Higher metabolites/nutrient signaling:


    2412882 -- histamine stimulated by galactosamine


    12716017 -- ALC and myo-inositol increase creatine phosphate.


    7191117 -- DA stimulates fucose and mannose incorporation into glycoproteins in hippocampus


    7907523 -- oral aminoglucose induced feeding suppression via histamine.


    11818483 -- PPAR review


    870654 -- leucine -- protein synthesis and nutrient signaling -- depressed food intake)


    10762040 -- alpha1 adrenergic receptor modulates rewarding effetcs of DA and opiates


    12199155 -- ALC prevents ATP depletion


    12609753 -- histamine (H1) and leptin


    9387093 -- acceleration of TCA cycle increases protein synthesis by increasing ATP.










    Protein Synthetic Machinery:



    11790952 -- muscle protein synthesis and amino acid availability


    11498025 -- requirements for protein synthesis -- differences in mTor linked pathways


    11242477 -- dietary protein and the IGF-1 system


    12423332 -- regulation of translation by nutrients -- review


    12501002 -- leucine, insulin, signal trasduction, exercise



    9597174 and 1772873 and 2661928 -- minerals and growth -- deficiency at cellular level before loss from muscle lowers protein synthesis


    3521317 -- Ca, Mg, thiol proteases and protein breakdown


    12388166 -- mTor and leptin


    12080086 -- mTor and IP3 dependence in cell growth


    9814971 -- leucine requires other amino acids for maximal activation of mTor -- effects linear at physiological concentrations


    6694002 -- leucine effects linear until maximal protein synthesis is reached


    12417714 -- TOP mRNA's controlled by IP3, not mTor


    12217881 – Essential amino acids and protein synthesis



    Food and Mood



    11324170 -- Histamine (like leptin) blocks DA steorotypy


    11249972 -- DA and Histamine


    10683850 -- Histamine (like leptin) modulates striatal DA activity


    12417657 -- NE, DA, and cysteine


    10336518 -- DA as alpha 2c ligand (like NE) -- negative feedback mechanism


    11507683 – PGE1 increases beta-endorphin, which increases glucose disposal


    9443837 -- insulin downregukates alpha2 in CNS


    11919655 -- tyramine and octopamine -- compete for DA Transporter


    12573518 -- DA, insulin, leptin – CNS - food/reward/metabolic parameters


    11272151 – Histamine(1) necessary for leptin's effects


    11349397 -- augmentation of drug reward with dieting via DA(1)


    8205479 -- augmentation of drug reward with dieting – opiate/endorphin


    8947935 and 12387683-- more food and mood


    973122 -- tyramine conversion to dopamine via CYP-45- enzymes


    11897683 – DA(2) required for proper IGF-1 functioning


    11744219 -- DA and IGF-1

    10422653 -- 5-HT potentiates bradykin induced muscle pain




    Adenosine Triphosphate



    12351422 -- ATP and nutrient signaling


    12387821 -- adenine and methionine restore hepatic ATP and protein synthesis.


    2339278 -- ATP substrates


    12398110 -- ATP stimulates arachidonic acid release


    9595270 -- ATP as mitogen


    11509496 -- creatine reduces leucine oxidation 20% in men


    11018652 -- ATP, swelling, and Cl- channnels












    11125222 -- insulin, cell-swelling, and nutrient signaling


    12696593 -- cell-volume and insulin signaling


    11530937 -- diuretic increases proteolysis


    12688629 -- swelling releases ATP, activates Cl- channels

    8889186 -- proline as "compatible osmolyte”


    12355187 -- taurine as osmolyte


    11881930 -- .5% betaine as nutrient partitioner in pigs


    12563517 -- glutamine as nutrient signal equal to glucose, in importance


    12153571 -- glutamine synergistic with leucine/insulin in promoting anabolic state


    12001166 -- glycine-betaine, asparagine, and glycine as osmolytes


    11533303 -- glutamine and nutrient signaling, via cell swelling, in liver


    12606317 – Reactive Oxygen species mediate taurine release


    11500954 -- cell-swelling and proliferative signal transduction


    10806336 -- cell-volume and protein synthesis

    Minerals/Ion Transport

    10381146 -- Mg and Vanadate synergistic in glucose disposal


    11963837 -- increased Mg improves recovery of ATP and protein synthesis and NO after glucose-oxygen deprivation

    11831463 -- zinc in signaling, proliferation and differentiation of mammalian cells.


    10871879 -- Ca2+ transport in the Sarcoplastic Reticulum


    10071779 -- Calcium signaling and gene expression.


    9124303 – Arachidonic acid and Na+ channels


    8926370 -- ion transport -- correlations to cell volume, hormone actions, and metabolism


    3544865 -- ion transport systems during cell volume regulation


    1721542 -- swelling activates ion channels


    12688629 -- glucose, ion channels, and cell-swelling


    10893434 -- Ca2+ and muscle


    11509825 – reactive oxygen species, Ca2+, cell-growth and differentiation


    12440694 -- glucose, Na+, cell-swelling


    11015618 -- exercise and K+


    12611772 -- glutamine potentiates exercise effect on IL-6


    10233023 -- cytokine induced glucose uptake redox sensitive


    11257454 – Arachidonic acid, PGF2a, glucose uptake and adipose differentiation


    12581497 -- histamine and NO


    12600796 -- 5-HT, histamine, ATP, PGE1 and muscle pain


    10940341 -- fatty acids and the immune response -- review


    9928421 -- inflammation/immune response and protein synthesis -- review


    8781295 -- TNF-alpha increases glucose uptake


    9375864 -- cytokines stimulate connective tissue


    6053649 and 940231 -- 5-HT and skeletal muscle


    12205200 -- inhibition of prostaglandin and NO decreases blood flow from exercise


    11557312 -- vitamin C and NAC increase exercise induced muscle damage


    9839076 -- exercise and cytokines


    11303145 -- exercise and IL-6 (produced locally)


    10762721 – Arachidonic acid and cell-swelling

    2nd Messengers/signal transduction


    11493020 -- IP3 essential for protein synthesis and glucose uptake


    9932214 -- IP3, insulin, cell growth, and anti-apoptosis


    12115906 -- alpha1 adrenergic activation increase IPs 8-fold


    10720331 -- IPs and gene expression


    8626564 -- inositol, Na+, glucose -- uptake/transport


    12457379 -- amphetamine increases IP activity


    1575723 -- insulin mediators


    9165224 -- IPGs as insulin mediators


    10212830 -- IPGs and growth factor signaling

    Anti-oxidants and co-factors



    11050172 -- thiols and redox


    10491755 -- lipoic acid prevents H2O2 downregulation of glucose uptake -- vitamin C and E unable


    11976222 -- ALC and lipoic acid


    11792699 -- free radicals down-regulate PPAR-alpha -- anti-oxidant protects


    12071973 -- cellular stress inhibits protein synthesis.


    10842745 -- Cellular thiols and redox-regulated signal transduction.

    6231057 -- vit E protects Ca2+ transport system against oxidized free fatty acids


    7547850 -- lipid peroxidation with fish oil and depletion of Arachidonic acid stores blocked with vitamin C and selenenium







  2. Big Motherfucker

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    Analects IX



    Puttting "super" in front of the name of your training method doesn't lead to supercession of your peon status at my gym. Furthermore, following a superslow protocol doesn't give you the inalienable right to occupy a station for 20 minutes.

    --- Ras


    Don't ask me how I can stay so thin while you are eating a donut.

    --- Icequeen


    A chest press should, in no way, involve the hamstrings or the lower back.

    --- str8flexed


    Admiring a work of art is not narcissism. Caring for it is not shallow.

    --- dawza


    Food, for the obese, is a substitute for sex. No choice in the matter does a bag of chips have, regardless of your appearance -- the same does not hold true for a person.

    --- Dante

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