Q & A: Growth Hormone-Releasing Agents Show Promise, with More Options Coming

Q & A: Growth Hormone-Releasing Agents Show Promise, with More Options Coming

Solid evidence is accumulating that certain amino acids can enhance beneficial growth hormone activity in the body, boost immune function and produce numerous anti-aging effects. Most promising is ongoing research on "secretogogue" therapy, that trigger the body's own growth hormone.

Q: Your article on human growth hormone (HGH) therapy in the June issue of Life Extension magazine really made me want to take it. I'm in my early 60s and the effects of aging are really starting to set in. The before and after photos you included in the article were especially impressive. The problem I have, in addition to the high cost of HGH therapy, is the necessity of giving myself injections frequently. The idea of sticking myself with needles isn't very appealing. How effective are the growth hormone-releasing nutrients discussed in the article in raising IGF-1 levels?

A: It's hard to say. There have been no studies comparing, on the one hand, the ability of nutrients to raise Insulin Growth Factor-1 levels, with, on the other hand, the ability of growth hormone injections to do the same thing (IGF-1 levels measure growth hormone activity in the body). Nor have there been studies to determine if the muscle-building, fat-loss (and other) benefits of HGH injections can be produced by taking GH-releasing nutrients.

Still, there is solid evidence that amino acids such as arginine, ornithine, lysine and glutamine can boost IGF-1 levels in humans, and that natural growth hormone-releasing formulas containing combinations of these nutrients are more effective in enhancing growth hormone activity than single nutrients.

A recent study of the effects of oral DHEA (dehydroepiandrosterone) intake (50 mg/day for 20 weeks) in the Journal of Gerontology (Series A, 52:1, 1997) showed that DHEA increased IGF-1 levels by an average of 20 percent, while also boosting various measures of immune function. Since there have been studies showing that DHEA can produce many of the same anti-aging effects as HGH therapy (including fat-loss and muscle building), you might try taking 50 mg of DHEA in addition to a good growth-hormone-releasing nutrient formula in an attempt to match the anti-aging benefits of growth hormone therapy.

Anyone starting on a regimen designed to boost growth hormone activity by taking growth hormone-releasing nutrients and DHEA should be tested regularly under the supervision of a physician for DHEAS and IGF-1 levels, as well as for other tell-tale signs of potential benefits such as immune function tests. Standard blood chemistry tests, which examine such functions as blood glucose, cholesterol and triglycerides, are also a good idea. You might also want to be tested from time-to-time on measures of strength, endurance and mental function.

The Life Extension Foundation may soon be funding a controlled clinical trial of the effects of HGH releasing nutrients and DHEA on age-related functions in middle aged and older persons, but until that time comes, we will be relying on the published results of other studies, and the results our members report from their own experiences with such regimens.

In a few years, there may be other options. Several pharmaceutical companies, including Merck and Wyeth-Ayerst, are currently testing compounds called secretogogues that trigger the release of growth hormone from the pituitary gland in much the same way as the body's own GH-RH (growth hormone-releasing hormone).

Another future option may be once- or twice-a-month injections of biodegradable polymers carrying human growth hormone, which will release HGH slowly and gradually into the body at consistent levels.

This approach would provide the direct benefits of HGH therapy, without the need for frequent injections. Genentech, one of the manufacturers of growth hormone in the United States, has contracted with Alkermes, a research and development company in Cambridge, Mass., to develop such a slow-release injectable product.

Q: Why is so much research money being spent on the prevention and treatment of age-related diseases, and so little being spent on aging itself?. Wouldn't a better research strategy be to focus spending on methods to control the aging process?

A: Yes. Absolutely. The No. 1 one cause of death in the United States today is aging, even though it is never mentioned on death certificates. Aging sets the stage for killers such as heart disease, stroke and cancer by progressively weakening us as we grow older. For example, aging is the greatest risk factor for heart disease.

A 50-year-old man has a 200 times greater chance of dying of a heart attack than a 20-year-old man. An 80-year-old man has a 2,000 times greater chance of such a fatality than a 20-year-old. This kind of exponential increase in risk cannot be explained by factors such as elevated cholesterol, homocysteine and blood pressure. In fact, an 80-year-old with none of these risk factors would have a significantly greater chance of dying of a heart attack than a 20-year-old who suffered from all of them.

The reason is simple. The 80 year-old has a greatly weakened and degenerated heart and blood circulation system, even if he has eaten right, exercised all his life never smoked, and taken heartprotective nutrients such as coenzyme Q10 vitamin E, vitamin B6 and B12 TMG (trimethylglycine) and magnesium. It isn't that such a healthy lifestyle doesn't reduce the risk of a heart attack; it does, in spades. It's just that there is simply no substitute for being young. While a 20-year-old with bad habits has a good chance of dying before he reaches 60, the 80-year old with good habits is virtually certain to die long before the same time span elapses.

The value of biological youth can be seen clearly if you consider that an 11-year-old is almost indestructible (in terms of risk). For every 10,000 11-year-olds, only about two will not make to the age of 12. After that, however, the risk of dying doubles at regular intervals until, by age 100 (if you make it that far), the risk of dying in the forthcoming year is about 50/50. This progressively increasing age-related risk is expressed in terms of a greater and greater risk of crippling and killing diseases. Conditions such as Alzheimer's disease, osteoporosis, Parkinson's disease and stroke almost never occur in young people. However, after age 40 the risk of a wide variety of chronic diseases doubles about every five to seven years.

Americans over 65 account for more than one-third of healthcare spending in the U.S. Yet the National Institutes of Health only spends about 7 percent of its budget on aging-related research, and only a very small fraction of that on interventive research aimed at gaining control over the aging process.

That's why the focus of the Life Extension Foundation is in finding therapies to slow down or reverse aging. We view any health measures short of this to be merely ways of buying time, so that we can benefit from anti-aging breakthroughs in the future to enable us to become biologically young again. No matter what we do to prevent or cure individual diseases, we'll still be faced with the progressive decline in physical and mental function caused by aging, which moves us inexorably towards death. On the other hand, advances that make us biologically young again will pull us back from the decline towards death. The younger we become, the further back from death we will find ourselves. When we achieve perpetual youth, the decline towards death will cease entirely, and we'll have the potential of living in good health for centuries.

Q: What are biomarkers of aging? I've heard this term a number of times in the last few years, but don't know what it means.

A: Biomarkers of aging are functional or biochemical changes that reflect the aging process. A number of biomarkers of aging have been proposed, but none has yet been established. Their purpose is to provide a way of measuring the rate of aging over a relatively short period of time in order to assess the ability of agents or regimens to slow down, postpone, retard or reverse the aging process.

The need for a short-term method of measuring the rate of aging arises because the only currently accepted method of doing so requires the extension of maximum lifespan. This kind of evidence takes years to produce in rodents. The lifespan studies being funded by the Life Extension Foundation, for example, are just getting underway after more than six months of planning. Since the long-lived mice being used will be only six months of age when the studies begin, it will take more than three years to determine whether any of the agents being tested can extend maximum lifespan.

Even if we find that one or more of the agents we are testing extends maximum lifespan significantly, we still will not know if this will happen in primates, including humans. For more than 65 years, we've known that calorie restriction can extend maximum lifespan and slow aging in mice and rats. It is only in the last decade that studies -- one at the National Institute on Aging's Gerontology Research Center in Baltimore, the other at the University of Wisconsin in Madison -- have been instituted to determine whether calorie restriction can extend maximum lifespan in monkeys. Although prelimanary results from these studies indicate that the same anti-aging changes that occur in calorically-restricted rodents are occurring in the experimental monkeys, it still will be another 20 years or so before we have any idea whether calorie restriction can extend maximum lifespan in monkeys.

Lifespan studies are completely impractical in humans because of the length of the human lifespan. The investigators for a human lifespan study would probably all be dead long before it was completed. Thus, the need for biomarkers of aging that can be used to measure the rate of aging in a few years rather than in decades.

The most promising approach in the search for valid biomarkers of aging is to find functions that decline (or are elevated) markedly with advancing age in various species, including humans, and then determine if this trend is reversed in calorie-restricted animals. According to these criteria, a good candidate for a biomarker of aging would be DHEA Sulfate (DHEA-S), the compound that DHEA is converted into when it enters the body. DHEA-S levels decline markedly with age in humans and rhesus monkeys. In addition the age-related decline of DHEA-S occurs twice as fast in monkeys than in humans, which may reflect the shorter lifespan of monkeys. Finally, calorie restriction, which extends lifespan and slows aging in rodents, also slows the age related decline in serum DHEA-S levels in these animals. These findings suggest that any agent that raises DHEA-S serum levels in humans, such as DHEA, could be slowing aging in humans.

Q: A couple of years ago, I heard about a hormone called leptin, which was reported to produce dramatic weight-loss by affecting the brain's regulation of food intake. I haven't heard anything about leptin recently. What's the latest word on leptin?

A: In 1995 the excitement over leptin as a hormonal regulator of weight was based upon the theory that leptin is secreted by fat cells to reduce appetite when a person starts to put on weight. The problem with this theory is that most people do not experience a reduction in appetite when they put on weight. In many people, the more they eat, the hungrier they become.

A new study provides evidence for a new theory of how leptin works. In this study by Roger H. Unger and colleagues at the University of Texas Southwestern Medical Center in Dallas, the human gene for leptin was added to rats, which then exhibited unusually high blood concentrations of leptin. The findings of this study were reported in the April 29 issue of Proceedings of the National Academy of Sciences.

When this occurred, the animals began to get slimmer and slimmer, until almost all fat disappeared from their bodies. This slimming effect was so dramatic that the scientists suspected that something other than appetite suppression was involved. They proceeded to find that cellular concentrations of triglycerides were significantly lowered in rats with extra leptin. Moreover, in test tube studies, leptin reduced the triglyceride (fat molecule's) content of rat pancreatic beta islet cells.

Scientists have found that people with diabetes usually have abnormally large concentrations of triglycerides in their beta islet cells, which reduce the ability of the pancreas to produce insulin. This new study suggests that leptin could be an effective treatment for diabetes, as well as a potent fat reducing agent.

Leptin is not available to the public for weight loss, and it may be many years before it becomes available. However, there is a product available now called Hydroxycitric acid or HCA, which also has been shown to help suppress appetite and reduce the fat content of cells. Extra fat is produced within the body when glucose (blood sugar) from excessive calorie intake is converted into acetyl coenzyme A via a metabolic pathway involving the enzyme ATP-citrate lyase, and then into trigylcerides, which are stored in fat cells. HCA inhibits this process by binding to ATP-citrate lyase to reduce the production of acetyl coenzyme A, which, in turn, reduces the body's production of fat and cholesterol. HCA also increases the ability of the liver and muscles to synthesize and store glycogen, which helps suppress appetite. HCA also is combined with chromium, which reduces resistance to the pancreatic hormone insulin to promote fat loss. Insulin resistance is common in overweight people.

Life Extension Foundation.

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