Anti-Aging effects of GH/IGF-1 by Ronald Katz, MD

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    ANti-Aging effects of GH/IGF-1 by Ronald Katz, MD


    Passages taken from "Grow Young With HGH" by Ronald Klatz, MD, president of the Academy of Anti-Aging Medicine.

    The most abundant hormone made by the pituitary gland is human growth hormone, also called somatotrophin. Growth hormone production hits its peak during adolescence. Most HGH is secreted into the bloodstream in brief bursts, and most HGH secretion takes place during the early hours of REM (deep) sleep.

    Once in the bloodstream, human growth hormone stays there for only a short time, only a few minutes, just long enough to stimulate its uptake into the liver, where it is then converted into growth factors. The most important of these growth factors is called IGF-1, short for Insulin-like Growth Factor-1. IGF-1 is also known as somatomedin C.

    Growth hormone exerts its actions either directly or indirectly through its intermediary insulin growth factors (IGF-1) to every organ system of the body. Almost nothing escapes its magic touch. In the same ways that it grows the bones of young children, it increases the size of most organs and tissue. Even the brain is affected. The latest studies in animals show that it can regenerate damaged brain tissue.

    It is IGF-1, rather than growth hormone itself, which can vary widely through the day, that is used as a measurement of how much growth hormone is being secreted by the body. IGF-1 is directly responsible for most of the benefits and actions associated with HGH. IGF-1 is 10 times more potent than human growth hormone and is now under investigation as a separate drug for many of the same indications of human growth hormone. Phil Micans of International Aging Systems in London believes that IGF-1 will be the hormone of choice in a few years.

    HGH and IGF-1 Get at the Blueprint of Aging

    "The blueprint of aging is in the DNA under the hood of the telomere", the "clock" at the end of every chromosome that is shortened with each cell division, says noted plastic surgeon and antiaging researcher, Vincent Giampapa, MD, director of clinical research at the Longevity Institute International in Montclair, New Jersey. To actually reverse aging at the cellular level, we will need a substance that will restore telomere length and like a genie turn old cells into young ones. That is not yet available, although Giampapa believes it will be in less than a decade. Until then, growth hormone and its attendant hormone IGF-1 can do the next best thing, help keep the cell in as healthy a state as possible.

    The cell's ability to function depends on the genetic material, the DNA, in the nucleus of the cell which codes for all the proteins, hormones, and enzymes that make the cell run. The DNA is like an army under constant attack from oxygen free-radicals, ultraviolet light, the heat of the body, and other damaging factors. Although the DNA has the ability to repair itself, it falls down on the job with age, a victim of the same aging process that affects the cell. At the same time, damage is accumulating in the energy center of the cell, the mitochondria, which has its own DNA. Up until now, one of the few ways we could limit the damage to the DNA was to take antioxidant supplements such as vitamin C and E to bolster our own defenses.

    But, according to Dr. Giampapa and Thierry Hertoghe, MD, a physician specializing in hormone replacement therapy in Brussels, the latest European research shows that human growth hormone and IGF-1 can go further than antioxidants and can do what antioxidants cannot. Human growth hormone and IGF-1 act like carriers to bring the cell the raw materials it needs for renovation and repair. IGF-1 launches the delivery of the nucleic acids, DNA and RNA, right into the cell nucleus, where the DNA resides. The nucleic acids are used to repair damage to the DNA and stimulate cell division. Growth hormone initiates the transport of amino acids, the building blocks of protein, and nucleic acids into the cytoplasm of the cell, the area outside the nucleus. This includes the cell membranes and intracellular organelles, such as the mitochondria. In this way, human growth hormone and IGF-1 don't just minimize the damage to the DNA and cellar structures, they help heal the cell and the DNA. These two hormones actually treat the blueprints of aging.

    Information on IGF-1

    IGF-1 is the other end of the growth hormone chain, the downstream player that actually exerts most of the effects we associate with human growth hormone. IGF-1 is causing a great deal of excitement among two groups, researchers who are exploring its vast potential and bodybuilders who are already using it and claiming eyepopping gains in muscle.

    IGF-1 More Potent Than Human Growth Hormone

    Human growth hormone exerts most of its effects through IGF-1. Therefore, it is not surprising that IGF-1 injections will do for you what human growth hormone does--and then some, according to its proponents. It increases lean body mass, reduces fat, builds bone, muscle, and nerves. By taking it directly, you bypass the pituitary gland, which may be "burnt out" with aging.

    IGF-1 appears to be even more potent than growth hormone in its anti-aging action. According to Keith Kelly, Ph.D., who did the work showing that growth hormone reversed the shrinking of the thymus, when he does his experiments on cells in culture, only IGF-1--and not growth hormone-- works. But both IGF-1 and growth hormone work in the living animal. "I know that both growth hormone and IGF-1 are substantially elevated in the old animals treated with growth hormone," he says, "but my prediction is that the main player is going to be IGF-1."

    IGF-1 and It's Potentials

    IGF-1 Preventing Brain Aging and Disease
    One of the spectacularly exciting uses of growth hormone and IGF-1 may be to prevent and treat the effects of brain aging. In an experiment that has momentous implications for brain injury, stroke, aging, and neurodegenerative disease, a team of scientists in New Zealand showed that IGF-1 can stop the death of cells in the brain. Barbara Johnston, Peter Gluckman, and their colleagues at the University of Auckland found that injections of IGF-1 given 2 hours after brain injury in fetal lambs rescued the damaged neurons and salvaged cells that would otherwise have died during apoptosis, which is the programmed cell death that is believed to cause the loss of brain cells for up to 3 days after the original injury. The treatment was effective in stopping the cell death throughout the brain, including the hippocampus, the cortex, the areas associated with thinking and memory. The treatment was also effective in the striatum, the part of the brain that plays a role in Parkinson's disease in humans. IGF-1 replacement was also found to reduce seizures in animals with brain damage.

    These researchers also suggest that IGF-1 might be used to inhibit the effects of neonatal hypoxia during birth (lack of oxygen to the brain) which can leave a baby with permanent brain damage. If IGF-1 can stop the programmed death of cells, then this opens up a world of undreamed-of-possibilities. For instance, the programmed death of cardiac cells after a heart attack leaves the victim with a heart full of dead tissue that before could not be repaired. Brain tissue is destroyed due to a stroke (CVA), and this cell death many times leaves the victim unable to walk, talk, or think clearly. It may also play a role in other neurodegenerative diseases such as Alzheimer's disease, muscular dystrophy, and multiple sclerosis. For the first time we may have a weapon against death at the cellular level.


    IGF-1 Improving Glucose Metabolism
    As its name indicates IGF-1, or insulin-like growth factor-1, has similar properties to insulin, and it has been shown to improve blood sugar profiles in type 2 diabetic patients. High doses of growth hormone have been shown to increase insulin resistance, but IGF-1 administration actually normalized the insulin resistance in a group of healthy volunteers.

    In the latter study, Nelly Mauras and Bernard Beaufrere of the Nemours Children's Clinic in Jacksonville, Florida, were looking at several different things: the effect of IGF-1 on protein metabolism; its ability to stop the protein-wasting caused by glucocorticosteroid drugs like prednisone, and its effect on insulin and glucose metabolism. They divided the volunteers into three groups who got one of the following: IGF-1 alone, IGF-1 plus prednisone, and prednisone alone. The study found that IGF-1 at 100 micrograms per kilogram of body weight given twice daily enhanced the body's protein metabolism in the same way as growth hormone. Like growth hormone, it markedly decreased the protein breakdown in the volunteers who were taking prednisone. But whereas growth hormone in an earlier study caused carbohydrate intolerance and insulin resistance when given in combination with prednisone, IGF-1 did not cause these diabetes-like effects. Instead, those subjects who received IGF-1 along with prednisone had normal glucose metabolism. This was remarkable, say the researchers, in light of the fact that glucocorticoids are known to suppress circulating insulin and decrease insulin sensitivity. As a result of this and previous studies, the researchers believe that IGF-1 offers promise in the treatment of protein catabolic states, such as patients who require IV feedings after surgery.


    IGF-1 Helping Diabetes
    Two 1997 double-blind clinical studies showed that recombinant IGF-1 injections can markedly reduce the need for insulin by up to 45% in patients with insulin-dependent diabetes mellitus. One study involved 8 adults between ages 24 and 49 and the other 43 children and adolescents between the ages of 8 and 17. In the adult trial, IGF-1 also lowered the total cholesterol and triglycerides after only four days of treatment.

    While these were short term trials lasting nineteen days and four weeks, respectively, that fact that the insulin requirement dropped markedly and there were no serious side effects make IGF-1 a promising drug for the treatment of diabetes. While it does not do away with the need for insulin, it improved the control of blood sugar and thus may help prevent the dire complications of diabetes, including heart disease, blindness, and peripheral nerve damage that can lead to amputation.


    IGF-1 Regenerating Nerves
    Another exciting potential use of IGF-1 is in the repair of peripheral nerve tissue that has been damaged by injury or illness. If a nerve is torn in the arm or leg, it means that the connection to the muscle may be impaired, and as a result there is loss of movement and the muscle atrophies. While peripheral nerves can regenerate to some extent, severe tears of more than a few millimeters may result in permanent injury. Now IGF-1 has repaired and reconnected severed nerve endings of up to a distance of 6 millimeters, a feat previously unheard of.

    Swedish scientist Hans-Arne Hansson of the Institute of Neurobiology at the University of Goteborg found that IGF-1 in combination with other growth factors could stimulate even more dramatic regeneration. "IGF-1 by itself and in combination with other growth factors is likely to be of importance in promoting healing and repair processes in clinical practice within a few years," he writes.

    In studies of cells in culture and in animals, IGF-1 has been shown to have remarkable effects on the spinal cord motor neurons. It increased motor neuron activity in spinal cord cultures by 150 to 270 percent. And it significantly decreased programmed cell death in developing chick embryos. In animal studies, it enhanced the sprouting of axons of the spinal cord motor neurons. And it increased intramuscular nerve sprouting a whopping ten fold when it was given to normal adult rats. In fact, according to a group of researchers at Cephalon, Inc., in West Chester, Pennsylvania, IGF-1 may be the "long-sought endogenous motor neuron sprouting factor."

    The implications of this work for helping people is nothing short of mind-boggling. If IGF-1 can regenerate spinal cord motor neurons, it may be useful in treating amyotrophic lateral sclerosis (ALS), a devastating disease in which the loss of spinal cord and cortical motor neurons results in complete paralysis and death. It may also be useful for peripheral neuropathies, such as Charcot-Marie-Tooth syndrome.

    John Wittig, MD, of UCLA has been using IGF-1 to prevent AIDS wasting in HIV infected patients. IGF-1 may allow more aggressive chemotherapy of certain cancers, since drugs like vincristine and cisplatin can cause peripheral neuropathies at higher doses.


    The Growth Factor Army
    IGF-1 is only one of the body's many growth factors that are now being identified, isolated, and cloned using genetic engineering technology for use as drugs. As growth factor researcher Eric Dupont, Ph.D., says, "Growth hormone is the general and growth factors are the foot soldiers." Growth factors function like hormones, hooking onto the receptors of cells and sending a biochemical signal across the cell's interior. Whereas hormones usually send long distance messages, growth factors for the most part do local calls.


    IGF-1, The Bodybuilder's Dream
    A number of world-class bodybuilders are using IGF-1 and reporting massive muscle magnification of up to 20 pounds. An article in Muscle Mass 2000 trumpets IGF-1 as "Possibly the Most Potent Bodybuilding Drug Ever!" According to author T.C. Luoma, "IGF-1 is out there on the streets of America right now; it's being sold out of the trunks of cars in Venice and brown paper packages containing it are being discreetly handed out at Southern California gyms." While there are no controlled studies supporting the musclemen's claims, the anecdotal evidence is building up. "Bodybuilders are claiming they are experiencing drops of 5% body fat in a month, while increases in lean body mass and strength are 'incredible.' Statements like, 'It's the most wonderful stuff in the world, and 'I couldn't believe it man' are the norm."

    There are skeptics, such as Mauro Di Pasquale, MD, an expert in performance-enhancing compounds, but there is a rationale for the belief that HGH taken with IGF-1 will work better. There is a feedback mechanism between the human growth hormone in the pituitary gland and the IGF-1 in the liver. The human growth hormone stimulates the release of IGF-1, but when the levels of IGF-1 rise to a certain point in the circulation, it signals the shutdown of growth hormone. But there is a lag time in all of this, which means that growth hormone levels increase at night and IGF-1 levels increase during the day. Bodybuilders hope that taking the two together will have a double-fisted effect on protein synthesis
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    excellent read bobo.
    I think we'll be seeing a couple cycle threads pop up here with igf-1 from the guys who've got the extra bucks to try it
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    Bobo,
    First off great read.
    Playing Devils Advocate, Could you start a thread with articles listing the possible dangers and side effects of IGF-1 and GH.
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    Here's one from T-mag in which Cy Wilson tears it apart. The problem with this article is that the studies he references actually work against his arguement.

    Also his arguement works against the use of steroids or any substance that increases IGF-1 production. This is also the case against Tren as it seems to be the steroid that increases hepatic IGF-1 the most. Another problem is that the distended belly and increase in growth of organs is much more the cause of very high doses of GH for prolonged peroids of times as this does not have a negative feedback loop like IGF-1. Exogenous IGF-1 looses its effectiveness somewhere around 30 days. GH does not have this limitation and continuous use of very high doses for prolonged peroids of time cause problems. Just like steroids, if you use responsibly you won't have any problems.


    IGF-1: Worst Bodybuilding Drug Ever?

    Q: What ever happened to IGF-1? It was talked about in 'roid books in the early '90s but you don't hear much about it now, except for a few sleazy supplement companies who are using the name.

    A: IGF-1 can allow for hypertrophy of muscle. Will it do such a thing when administered to humans? Yes. However, the gains seen really arenít spectacular. More often than not, they donít even come close to gains seen using androgens.

    For the most part, people should realize that IGF-1 is primarily responsible for GHís anabolic effects in skeletal muscle as well as cell proliferation, leading to enlarged internal organs and increasing the risk for cancer dramatically. Oh, and this most certainly includes Long R3 IGF-I as I know some people will try to argue that it's much safer.

    Well, in order to give you the total picture, Iím going to go over some basic molecular biology as well as list the direct evidence we have concerning the side effects of IGF-1 and yes, that includes Long R3 IGF-I.

    First, people should understand that in the human cell cycle, growth requires growth factors in general. Seems simple enough. The next thing people need to understand is that for a normal cell, death is something that'll inevitably occur via loss of telomerase or apoptosis (programmed cell death). Again, I canít overemphasize enough that the default pathway in humans is death, not growth. (Reassuring, isn't it?)

    Now, when you hear of cancer, malignant cancer, people tend to think of uncontrolled cell division. Essentially though, these transformed cancerous cells are immortalized. Now, many changes are required for this to occur (i.e. increased telomerase, increased bcl-2, increased myc and decreased p53). In the development of cancer, we tend to think of carcingogens consisting of both initiators and promoters. For instance, some initiators are UV radiation and tobacco smoke, usually causing DNA damage or mutation, whereas promoters tend to stimulate cell division. A few examples are phorbol esters, hormones (e.g. estrogens) and yes, growth factors.

    Now, keep in mind both events, initiation and promotion, are required for the development of malignant cells. As a side note, viral infection can also lead to the two events, but I digress. Anyhow, normally a cell serves its purpose and then dies via apoptosis. However, malignant cells donít undergo apoptosis. They are, as I said before, immortal. The normal triggers to apoptosis are DNA damage, loss of cell-matrix contact, loss of cell to cell contact, and last but most certainly not least, lack of growth factors.

    When you introduce growth factors, youíre providing the catalyst for cancer formation, so to speak. Letís say, for instance, you get many sunburns during your lifetime. Now, letís say that one cell has its DNA damaged or altered. This, in and of itself, isnít too much of a concern as this is only one part of the equation, the iniation. The second part is the promoter (including growth factors).

    Well, letís imagine we introduce growth factors to the cell which has damaged or mutated DNA and it then begins to divide at a more and more rapid rate until it wonít stop. Voila, you have a tumor, which is now capable of even faster growth as well as being invasive (able to invade surrounding tissues) and metastatic (able to cause growth in completely unrelated and distant tissues) in regard to other tissues.

    In other words, you now have a malignant tumor, which we commonly refer to as cancer. The fact is, cancer stems from just one cell, just one cell, which begins to divide uncontrollably. People often talk about GH and the side effects thereof, but what most donít realize is that many of those side effects aren't necessarily mediated by growth hormone but by IGF-1.

    Many people may go their whole lives with some DNA damage (or mutation rather) and never have cancer, but with the addition of growth factors, youíre asking for trouble. Even more specifically, you can increase the risk of developing rare forms of cancer, like sarcomas, which are tumors commonly found in connective tissues (i.e. muscle, bone, cartilage, etc.)

    Okay, now on to the more cosmetic side effects. With Long R3 IGF-I, it was shown to stimulate growth of the gastrointestinal tract. IGF-1 actually had no effect on body weight and wet tissue weight of the small and large intestine, whereas Long R3 IGF-I resulted in a 20% increase in the weight of the small and large intestine. This is what's causing a "GH gut" although using Long R3 IGF-I is much, much worse than using GH.

    Something else to keep in mind is that Long R3 IGF-I was shown to be even more potent than IGF-1 in inhibiting apoptosis and thus its potential for causing cancer is many times greater.

    Another idea is that IGF-1 may also keep telomerase activity high, which as we noted previously is a contributing factor for the loss of regulation in terms of cell division. In other words, it again can substantially increase the risk for developing cancer. Long R3 IGF-I was shown to increase telomerase activity in human prostate cancer cells, whereas IGF-1 had no effect.

    So, when I tell you to stay away from IGF-1, Iím actually referring to Long R3 IGF-I as itís what's most commonly circulated and used. Although both aren't something a person should use, Long R3 IGF-1 is probably the worst choice you can make.

    So, unless youíre an IFBB pro who consistently places in the top ten at popular contests, you should forget about using IGF-1, or specifically the analogue of IGF-1 called Long R3 IGF-I. Itís really not worth the risk. This, out of all the compounds that bodybuilders may use, is probably the worst in terms of potential side effects.

    If you want a true distended belly and increased risk of cancer, be my guest. (47-52)
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    as much as I would love to believe that igf-1 is even 10% as terrific as that first article states, I think it is fairly biased.
    while igf-1 may have it's medical applications, to toute it as something that can be used to fight aging demands that you ignore a lot of evidence that high gh/igf levels are linked to shorter maxium life spans in every animal study i have ever been aware of and that administering those hormones in significant dosages can cause medical complications that may very well reduce mean life span (i.e. cancer).
    I'm going to bed now, if you need me to dig up some studies, I guess I am somewhat obliged to back up my opinion. There may be new data on this since last time I was into aging stuff (like a couple years ago), but I recall the existing data back then as being dissapointing and argueing against gh.
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    You can dig them up. Then I will show you where they were torn apart.

    And can you tell me how the first article is biased?
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    Also the studies on animals show a significantly different effect than in humans. It is anabolic in rats, catabolic in pigs (because it lowers endogenous GH, IGF-1, and insulin in pigs but not in rats).


    Also all the studies that involved cancer showed IGF-1 in any form to increase the growth of EXISTING cancer cells. THere is not one study showing that IGF-1 causes cancer. AAS/PH's or any growth factor have the exact same effect.

    So those are hardly conclusive.


    Another problem wiht the article is that it states L3 is riskier than rIGF-1. Studies show its actually the other way around becuase of the frequency of injections, and high amounts needed for rIGF-1. THis is actually what professional BB'ers used in the beginning because it was the only one available.
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    I think there's some research going on in the telomerase end of things that is very interesting and promising.

    Anybody see the demonstration on Scientific American Frontiers where researchers added telomerase to a petri plate full of aging and decrepit nematodes and then some old human cornea cells..and they were totally rejuvinated? My jaw hit the floor.

    Homing in on IGH-1 and telomerase could seriously mean tripling of human life span within our lifetimes. Freaky cool stuff.
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    Quote Originally Posted by comrade
    as much as I would love to believe that igf-1 is even 10% as terrific as that first article states, I think it is fairly biased.
    while igf-1 may have it's medical applications, to toute it as something that can be used to fight aging demands that you ignore a lot of evidence that high gh/igf levels are linked to shorter maxium life spans in every animal study i have ever been aware of and that administering those hormones in significant dosages can cause medical complications that may very well reduce mean life span (i.e. cancer).
    I'm going to bed now, if you need me to dig up some studies, I guess I am somewhat obliged to back up my opinion. There may be new data on this since last time I was into aging stuff (like a couple years ago), but I recall the existing data back then as being dissapointing and argueing against gh.

    You also have to remember that article is for older men in which IGF-1/GH levels are much lower and the typical doese would be considerably lower than an average BB'er. Like I've said all along, moderation is the key and high does for prolonged peroids of time in anything can cause problems. AS for Long R3, you can only use for 30 days anyway so in in a sense, its a built in safety mechanism.
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    Quote Originally Posted by bioman
    I think there's some research going on in the telomerase end of things that is very interesting and promising.

    Anybody see the demonstration on Scientific American Frontiers where researchers added telomerase to a petri plate full of aging and decrepit nematodes and then some old human cornea cells..and they were totally rejuvinated? My jaw hit the floor.

    Homing in on IGH-1 and telomerase could seriously mean tripling of human life span within our lifetimes. Freaky cool stuff.

    Yeah I read something similar. There is so much data I've been sifting through the past couple months its tough to remember it all.
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    Anybody see the demonstration on Scientific American Frontiers where researchers added telomerase to a petri plate full of aging and decrepit nematodes and then some old human cornea cells..and they were totally rejuvinated? My jaw hit the floor.

    Homing in on IGH-1 and telomerase could seriously mean tripling of human life span within our lifetimes. Freaky cool stuff.
    I missed that...do you have a web link to it?

    Damn, Id love to live to 255yrs old!! If I keep working at this crazy ass 60hr a week job Im at, it will take at least half that long before I bench 400

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    No, I'm afraid I don't. It was a PBS TV program a couple of years back. I'm sure it has to be in the literature somewhere but since its likely in the bio-chem or cell-molec realm it would take a while to search it out. There's no pub-med for lowly biologists that I know of..not one that is truly comprehensive anyway.
  

  
 

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