I really liked this article since I compared so many different studies. I have to stop reading so much because it keeps making me want to change my mind on my cycleI've seen alot of ques. about GH and cancer lately too, which this also touches base on. Hope you enjoy it
By: Michael Clark, Clinic Director
Most people think of HGH as the miraculous treatment for children doomed to dwarfism, which over the past 30 years has saved tens of thousands from this fate. The next great benefit of HGH therapy appears to be in the aging population. People with age related deficiency of HGH become fat, flabby, frail, and lethargic, lose interest in sex, have trouble sleeping, concentrating, remembering things, tire easily, and in general, lose their zest for life. With HGH, all these so-called signs of aging are reversed.
The following articles and information on Human Growth Hormone (HGH) are provided for your examination. At Natural Bio Health, we prefer to call HGH the “healing hormone” as this more appropriately describes its functions in the areas of preventive and anti-aging medicine. The more research that is conducted on this hormone, the more we find support for its use under the supervision of a medical clinic.
It should be noted that unlike certain hormones such as testosterone, thyroid and progesterone, where results can be seen in as little as 30 to 60 days, HGH is not a “quick fix. One can expect dramatic results – but only after a minimum of 6 to 12 months. Recent studies show that a decrease in body fat can take up to 12 months. The studies also show decreases in the incidence of diabetes and cardiovascular morbidity occur after 12 months.
In other studies, a full 12 months was necessary to realize the full effect of increased exercise strength and endurance (19% increase). Many studies show a decrease in cholesterol, apolipoprotein B, and increased HDL after 6 to 12 months.
HGH is a FDA Approved Drug
In August 1996, the FDA approved HGH for use in adult patients for the first time. Before this, it was only authorized for use to promote growth in HGH deficient children. The new indication is for "SDS," or somatotropin (growth hormone) deficiency syndrome, as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy or injury.
In effect, the FDA approval covers the use of HGH for anti-aging purposes since low levels of HGH or IGF-1 indicate a failure of the pituitary to release adequate amounts of this vital substance. In addition, the signs of SDS, such as decreased physical mobility, lower energy, higher risk of cardiovascular disease, are exactly the same as those seen in aging adults with low HGH levels. The FDA approval for HGH in adults means that any physician may now prescribe it to their HGH deficient aging patients without fear of practicing outside of conventional orthodox mainstream medicine.
Article written by Dr. Neal Rouzier, author of Healthy Aging
For years I have awaited the results of a study by Mark Blackman, M.D., once the Chief of Endocrinology at John Hopkins and now a director of The National Center of Complementary and Alternative Medicine at the NIH. I considered this physician to be the leader in growth hormone research, a superb scientist and an excellent speaker on HGH. The long anticipated results of his study on HGH appeared in the November 13, 2002 issue of JAMA. Dr. Blackman has studied hormones extensively and is a strong supporter of HGH for the prevention of deterioration that accompanies aging.
I was hoping that his study would put HGH on the front page of newspapers and quiet the fears and concerns of physicians who remain skeptical. Unfortunately, it didn't. In fact it made the situation worse. The good points of the article were that HGH was beneficial in increasing lean body mass, decreasing fat mass, increasing muscle strength and enhancing endurance. The problem was that HGH was termed dangerous due to side effects (edema and arthralgia) and the risk of causing diabetes in a few men. Past studies have shown that high doses of HGH can raise blood sugar and cause insulin insensitivity.
The purpose of this review is to dispel the fears, explain why the researchers found side effects, and to give a synopsis of the 300 plus articles I have recently and diligently reviewed. Keep in mind that this is just one study out of hundreds of studies and must be looked at accordingly. My systematic review will first summarize Dr. Blackman's article and secondly compare it with other studies.
Dr. Blackman's study reconfirmed what all other studies have shown: HGH and sex steroids improve body composition, strength, muscle mass, endurance and decrease visceral fat and total percent body fat. This comes as no surprise as this is precisely why we recommend HGH.
The problem was the high frequency of side effects: carpel tunnel pain, edema, arthralgias and glucose intolerance, are the identical dose-related, side effects that have been reported by previous studies. The starting dose of HGH used was 30 ug/kg or about 2.4 mg for an 80 kg man. This equates to a daily dose of 1mg/day, but it was given as the higher amount of 2.4 mg per each dose. The average dose we use is 0.2mg/day and increase to 0.4mg/day after one month. It is obvious that a much higher dose given less frequently should cause symptoms and it did.
Dr. Papadakis reported the same benefits and side effects in her article in the Annals of Internal Medicine five years ago. The problem in both studies is that they used HGH at such high doses and only three times per week! Anyone who has ever responsibly prescribed HGH would expect these types of side effects at such high doses. Many of us who prescribe HGH know that using smaller doses given daily will avoid such side effects. I have been teaching this technique to physicians for five years and rarely have I encountered problems. The rare side effects are eliminated by dose adjustment.
Out of the hundreds of physicians that I know prescribing HGH, I know of no one that prescribes HGH at this high of dose nor at only three times per week. Moreover, HGH manufacturers recommend daily injections, rather than one injection three times a week. The PDR also recommends that all HGH be dosed daily. If most doctors prescribe daily injections without problems as the PDR recommends, why do these world-renown scientists use high doses three times weekly? Simply because that is what had always been done in past studies.
To me, it seems absurd and a waste of time, money, and expertise to conduct a study using doses sure to cause side effects. Mitchell Harman, M.D., who co-authored this study, is aware that doctors throughout the world prescribe HGH daily and in smaller doses seemingly without problems and that this is the method that should be studied. However, in order to keep in concert with other studies, they continued to study HGH at the wrong dose and in the wrong method, in spite of a plethora of experience and information to the contrary. Had the dosing regimens been different, I'm sure the study would be viewed in a more positive light.
One must thoroughly understand HGH and the different dosing regimens to understand why this study is flawed. Hopefully one day a pharmaceutical company will give a grant to repeat the study using the correct and agreed upon dosing -- only then would the results truly reflect HGH therapy.
An interesting and significant change instigated by Dr. Blackman was to not study adults with HGH deficiency, but rather healthy adults. An article in JAMA 2000;284:861-868 showed that adults over age 40 typically have 75% less growth hormone than younger adults. Although by definition this is not a true deficiency, most of us consider 75% less hormone a significant decline.
All studies up until now have only studied adults with a confirmed laboratory deficiency, whereas Blackman studied everyday, normal adults, which happens to be the group most often found to be taking HGH. I can't help think that this study could have shined among the rest had it followed proper dosing. Medicine is anecdotal by nature and if patients have been successfully treated without problems, then it should be studied in that fashion, not in a way that has previously been shown to be problematic.
Since edema and arthralgia are dose related and can easily be corrected by dose adjustment, it's considered only a minor problem. But what about the diabetes issue? Most studies document insulin resistance for the first 3 months with normalization thereafter. Most studies also note a decrease in visceral fat in 6-12 months, which improves insulin sensitivity. Blackman's study was for only 6 months.
There are many studies documenting a significant decrease in cardiovascular disease, which is the overall goal. There are recent studies documenting improvement in HgBA1C, which indicates an improvement in diabetes, not a worsening as suggested by Blackman's study. Again, I believe that the incorrect doses and the short duration of the study are responsible for the few reported cases of glucose intolerance. I tend to trust the multitude of long-term studies showing no trend towards diabetes, only protection against diabetes.
I believe that Dr. Blackman should be criticized for several things in addition to the dosing of HGH. First he used injectable testosterone at 100mg every 2 weeks. This certainly was not physiologic, but necessary to assure compliance. Secondly, he did not allow his subjects to exercise.
Any athlete knows that HGH and testosterone greatly enhances strength and endurance when exercise is permitted. I'm sure Blackman's results would have been much better had exercise been allowed. Finally, Dr. Blackman should be embarrassed for using 10mg of the cancer causing medroxyprogesterone in the female subjects. First, 10mg far exceeds the average dose and second, Dr. Blackman should know the benefits of using natural progesterone over Provera.
Had I known their protocols in advance, I would have easily predicted the outcomes and could have written their paper for them. Even though there were great benefits from HRT use, I would have correctly predicted the side effects based on the high doses used and the incorrect method of administration. I would really like to design another study using the hormone replacement method that we use daily in our practice as opposed to the method they employed. Yet, that is the difference between clinicians and academicians. Unfortunately, because they have no insight into the inadequacies of this study, there are clinicians who will be hesitant to recommend HGH based on its conclusions. To me the study was worthless since it didn't tell us anything new and it made it more confusing for those unfamiliar with HGH and the appropriate treatment protocols.
An article by Lewis Blevins (The Endocrinologist 2002; 12:405-411) reviews HGH and the beneficial effects in muscle strength, exercise capacity, bone remodeling, psychological well-being, fat reduction, and many other factors that prevent cardiovascular disease. He comments on new dosing regimens that maximize the benefits of HGH while minimizing the adverse effects. The decrease in body fat took up to 12 months and resulted in a decreased incidence of diabetes and cardiovascular morbidity.
Many studies also show a decrease in cholesterol, apolipoprotein B, and increased HDL. A full 12 months was necessary to realize the full effect of increased exercise strength and endurance (19% increase). There was a 15% increase in bone density, greater than that typically seen with estrogen or biphosphonate therapy. Most importantly, there was significant improvement in quality of life and vitality.
Dr. Blevens, a professor of endocrinology at Vanderbilt, warns that HGH dose must be individualized. Doses are given daily to avoid side effects(!) and HGH is initiated at .1 to .2 mg/day (which is exactly what we do, yet what Blackman failed to do). Doses are then slowly increased monthly based on clinical response and blood tests. (Again Blackman did not titrate slowly, which accounts for the side effects). Dr. Blevens notes that the common side effects-edema, myalgia, arthralgia-are due to the anti-natriuretic effect of HGH. These symptoms are mild, dose-related and easily corrected by dose adjustment, and usually resolved in 1 to 2 months.
As the result of decreased visceral fat, increased lean muscle mass, and improved lipoprotein profiles, there was no evidence of increased risk of diabetes. The initial decreased insulin sensitivity was short term and was not a factor due to increased metabolism.
This was also shown in the meta-analysis study published in the New England Journal of Medicine (N Engl J Med. 1999;1206:24-34) that documented an increase metabolic rate of 6-11%. "Based on overwhelming evidence of efficacy and safety, the American Association of Clinical Endocrinology has recommended GH replacement therapy. Therapeutic monitoring should focus on resolution of symptoms and normalization of IGF-1 levels."
A recent study in Journal of Clinical Endocrinology and Metabolism (87:2725-2733, 2002) used HGH doses of .4 mg/day (typical of our dosing and much lower than what Blackman used). Again, there were significant changes in body fat and body composition. Echocardiography demonstrated improved cardiac output in both sexes. GH was well tolerated with side effects related only to transient edema and fluid retention. There were no cases of diabetes or glucose intolerance with this regimen.
Probably the best review of GH can be found in the official Journal of the Growth Hormone Research Society and the International IGF Research Society. A recent article (Growth Horm IGF Res.2002;12:1-33) reviews 273 recent articles on HGH. The authors very thoroughly reviewed glucose metabolism and insulin sensitivity. Most studies show initially reduced insulin sensitivity between months 1-6. Thereafter body composition improves and there is an increase in insulin sensitivity and improved glucose utilization, but only after six months. Again, Dr. Blackman's study was for 6 months only. Many of these studies also utilized high dose HGH, but found no increased risk of diabetes at the 12-month mark.
The studies lasting 1-4 years showed initial reduced insulin sensitivity. Yet, after four years, there was improved insulin sensitivity, lower glucose levels and no deterioration in glucose tolerance. The two longest studies lasting ten years showed no reduction in insulin sensitivity. There were also no changes in glucose, insulin levels, C peptide levels or glucose tolerance. In fact, most adults were insulin resistant, but the decreased fat, increased metabolism, and improved lean body mass, decreased their risk of diabetes. "Hyperinsulinemia (insensitivity) persists up to one year, however there are no long term adverse sequelae with no increase in the development of diabetes. There is no difference in incidence of diabetes from what would be expected in the general population."
I feel it would have been most appropriate had someone written an editorial review in JAMA based on the above literature to clarify the issues and prevent the misunderstanding that now exists. The lack of this editorial review is truly a disservice to physicians and patients who will now believe that HGH causes diabetes when in reality it does not. In fact, it prevents the metabolic syndrome X that causes diabetes and the initial worsening of insulin sensitivity that occurs in a few individuals as in Dr. Blackman's study.
Most importantly, this review in Growth Hormone and IGF Research assesses dosing and replacement regimens. Earlier studies investigating the effect of GH replacement in adults were based on doses used in children (unfortunately, Blackman's study made the same mistake). With time, it is becoming apparent that these protocols cause over-treatment with the resulting adverse side effects.
Some studies now are designed to use much lower doses to avoid the side effects (which makes perfect sense). Reduced doses resulted in the same beneficial outcomes with reduced side effects. Other studies utilized slower dose titration with even fewer side effects. One study found that the mean dose in men required to normalize IGF-1 was 0.2 mg/day, whereas in women it was 0.4 mg/day. With time it became routine clinical practice to titrate GH dose according to IGF response.
Johannsson et al demonstrated that slowly titrating GH dosing resulted in less side effects but similar clinical efficacy as compared to standard high dose regimens (how about that!). The Growth Hormone Research Society has published consensus guidelines for GH replacement. They concluded that dose selection should be at a low dose and then titrated according to clinical and biochemical response.
There is no gold standard for measuring GH replacement and the whole clinical picture needs to be taken into consideration, including IGF-1, to ensure correct management. Dr. Blackman did not follow any of these guidelines, thereby causing significant adverse effects by an inappropriate high-dose regimen. Thus, his results and conclusions came as no surprise. It is an absolute waste of resources to study HGH in this fashion.
Finally, data from KIMS, a pharmaco-epidemiological survey of 6000 patients receiving HGH, showed only 32 patients developing diabetes on HGH. Most of those patients were obese with a family history of DM. In the HypoCC long-term compilation study by Eli Lilly, 1881 patients were followed with control groups. There was no increased incidence of diabetes, malignancies or mortality while on HGH.
It appears as though physicians and the public alike have become anti-hormone due to media hype and sensationalism. Nevertheless, when our hormone levels fall, we deteriorate resulting in less energy and vitality with a greater risk from the illnesses of aging. The literature is full of data documenting health and feel-good benefits with less morbidity and mortality from hormone replacement.
Hormones should be carefully prescribed, monitored and adjusted to physiologic levels. Synthetic, non-bio-identical hormones, or chemically altered hormones (Provera, Progestins) should be avoided. All natural hormones have scientific, documented benefits at optimum, physiologic levels and detrimental health consequences at lower levels seen with aging. GH is no different.
Our hypocratic oath states we should "do no harm." However, by letting ourselves, and our patients, deteriorate when appropriate therapy is available is counterintuitive and indeed harmful. I hope the plethora of scientific studies supporting the use of GH is compelling and reassuring to you and that you can look at all of these studies objectively. Make the decision worthy of your patient's health and well-being.
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Originally Posted by Seattle Junk
