麻豆传媒

THE quest for muscles with more power knows no bounds. It began in the 1950s with American and Russian weightlifters injecting themselves with steroids. By the 1980s, natural substances such as growth hormone were the unscrupulous athlete鈥檚 choice. Now a new elixir rumoured to confer tremendous stamina and muscle tone is throwing its weight around in the gym. It鈥檚 called insulin-like growth factor-1 or IGF-1, and bodybuilders and powerlifters are frantic to get their hands on it. Despite its growing reputation as a potent anabolic agent, there are no laws controlling the sale of IGF-1 in the US or Europe. And no one is yet testing for it at athletic competitions.

鈥淎 couple of big name bodybuilders paved the way for IGF-1 use because they had tremendous results building muscle with it,鈥� says Peter Thorn, president of the US Powerlifting Federation. 鈥淚GF-1 is out there on the streets of America right now,鈥� says T. C. Luoma, editor-in-chief of Muscle Media 2000, a body-building magazine devoted to drug-enhanced strength.

鈥淚t鈥檚 being sold out of the trunks of cars in Venice [California], and brown paper packages containing it are being discreetly handed out at southern California gyms 鈥� most bodybuilders 鈥榢now a friend who knows someone who has a cousin鈥� who can get the stuff.鈥� And sports researchers think it likely that people in Europe are trying to pump up their muscles with IGF-1, too.

It鈥檚 no accident that all this is happening just as biomedical research into IGF-1 is taking off. Thousands of papers on IGF-1 have appeared in medical journals over the past few years. Researchers hope that the peptide will eventually be used to treat a number of disorders, including motor neurone disease and dwarfism. But at the same time, it鈥檚 clear that not all the IGF-1 produced by biotechnology companies is reaching the clinics. Manufacturers say they are having to institute elaborate safeguards to prevent this costly and scarce drug from being diverted to the black market (see Box).

IGF-1 can鈥檛 be knocked together in a garage with a bit of glassware and a smattering of high-school chemistry. It鈥檚 a naturally occurring peptide made up of a precisely structured chain of some 70 amino acids folded into a unique configuration. The peptide gets it name because about half of its aminoacid structure is identical to insulin and it can bind weakly to insulin receptors, as well as its own IGF-1 receptors on the surfaces of cells.

Like growth hormone, IGF-1 is essential for normal growth and development. Indeed the biological roles of the two are intimately intertwined. The traditional view is that growth hormone is produced by the pituitary gland, courses through the blood, and stimulates the liver to unleash IGF-1 peptides. These peptides then disperse and stimulate cells to divide and grow. But recent research suggests that growth hormone can also trigger a more localised release of IGF-1 in cartilage, muscle and other issues.

During normal development the effects of IGF-1 differ sharply from one tissue to another. In muscle cells the peptide stimulates the production of proteins and other cell components, while it mobilises fat for use as energy in adipose tissue. In lean tissue IGF-1 prevents insulin from transporting glucose across cell membranes. As a result the cells have to switch to burning off fat for energy. This effect of IGF-1 explains why some researchers are testing growth hormone, which stimulates the body to produce IGF-1, as a slimming drug.

Beefing up muscle cells while burning off fat sounds like a great recipe for athletic success. The catch is that not everything that stimulates tissue growth during development will work in full-grown healthy adults. Over the past decade it鈥檚 become clear that injections of growth hormone or of IGF-1 can help children with deficiencies in these substances to grow to a normal height. Growth hormone can also help adults with hormone deficiency to lose fat and gain lean tissue. And according to controversial research by Daniel Rudman, professor of geriatrics and gerontology at the Veterans Affairs Medical Center in Milwaukee, a six-month course of growth hormone can increase lean tissue and reduce fat in the elderly.

Already, clinics have sprung up in Mexico, Switzerland and the US devoted to selling growth hormone therapy 鈥� not to people with hormone deficiencies but to healthy individuals seeking greater strength and sex appeal in their golden years. Does it follow that injections of growth hormone, or its handmaiden IGF-1, could benefit healthy young powerlifters?

Here hard facts begin to degenerate into the flab of anecdote and opinion. According to Luoma, users are calling IGF-1 鈥渢he most wonderful stuff in the world鈥� for gaining muscle and losing fat. In Muscle Media 2000, an anonymous bodybuilder describes his experience with IGF-1: 鈥淚 got ripped. It was really noticeable. I stay pretty lean most of the time, but this took it to a different level. Veins in my abs, that sort of thing.鈥�

Luoma admits such reports are of dubious value. 鈥淢ost bodybuilders are using so many different drugs that it鈥檚 almost impossible to tell whether the effects are from the IGF-1,鈥� he says.

Nevertheless, some scientists do say that IGF-1 could be used to stimulate muscle growth in healthy adults. David Clemmons, an endocrinologist at the University of North Carolina, began to take the idea seriously in 1993 when he put four men and three women between the ages of 22 and 47 on a diet low enough in calories to cause muscle and other tissues to break down, a process called catabolism. Clemmons found that he could protect the subjects鈥� muscles from catabolism by giving them a combination of IGF-1 and growth hormone. And the combination was far more anabolic than either substance alone, he says.

Bodybuilders have apparently cottoned on to Clemmons鈥檚 work. 鈥淐ombining IGF-1 with GH is practised by some bodybuilders,鈥� says Luoma. Others seem to value IGF-1 more highly than growth hormone because it is the substance that does growth hormone鈥檚 work in the body.

Manufacturers of IGF-1 are anxious to distance themselves from claims that it has profound anabolic effects in athletes. Few want to see the name of a medically promising product tarnished by abuse stories, as happened with growth hormone.

鈥淭here鈥檚 no question that IGF-1 works brilliantly in rats,鈥� says John Ballard, managing director of GroPep Proprietary in Adelaide, an Australian-based manufacturer of IGF-1. 鈥淚t stimulates their growth, it reduces any wasting conditions from diabetes, kidney failure or removal of parts of the gut.鈥� The trouble is, it鈥檚 not very specific. When IGF-1 is injected into adult rats, non-muscle tissues also grow, such as in the thymus, spleen and kidneys. That, says Ballard, means IGF-1 is unlikely to have a selective anabolic effect on human muscles.

Black market

And just because IGF-1 slows down the progression of motor neurone disease doesn鈥檛 mean it works by directly stimulating muscle growth. More important here could be the drug鈥檚 ability to make new nerve fibres grow, thus renewing connections to muscle cells. Besides, the scarcity and expense of IGF-1 on the black market would make it hard for most people to obtain significant amounts. A single vial containing about 0.1 milligrams of IGF-1 has a black market price tag of $600. It would take 10 or more such vials per day on a continuous basis to produce a biological effect, says Ballard.

However, some sports authorities, such as USPF鈥檚 Thorn, believe that there are well-paid, professional athletes, not to mention nations hungry for Olympic success, who could support such an expensive habit. And the fact that IGF-1 is so rare and expensive makes it highly prized.

The high price of IGF-1 may have so far protected many users from the dangers of overdose. Large doses of IGF-1 will trigger a dramatic drop in blood sugar levels just as surely as an overdose of insulin. And by prolonging the lives of damaged cells that would otherwise die in the body, chronic abuse of IGF-1 could in theory increase the risk of uncontrolled cell growth, and hence cancer. Excess growth hormone has also been linked to side effects, including high blood sugar levels, carpal tunnel syndrome and the development of enlarged hands, feet and overly prominent jaws.

Clemmons warns athletes not to use IGF-1 and growth hormone to increase muscle mass because of their 鈥渉igh side effect profile鈥�. Typically the dose that is needed to produce an anabolic effect on muscles is perilously close to the danger zone. Among the side effects are facial nerve paralysis and a fluid build-up that can cause a dangerous oedema of the brain. 鈥淚 don鈥檛 think they鈥檇 see a tremendous increase in strength,鈥� says Clemmons. 鈥淚 think they鈥檇 start to get themselves into trouble so quickly that they probably would quit doing it or hurt themselves to the point where they couldn鈥檛 compete.鈥�

Athletes intent on abusing anabolic drugs should stick with testosterone, which is cheaper and safer, says Clemmons. 鈥淒ollar for dollar, you鈥檇 be a whole lot better off taking steroids.鈥�

Except, that is, when it comes to drug testing in competitions. For while sports authorities are beginning to test for growth hormone, tests for IGF-1 are still at the planning stages. The International Olympic Committee has banned all peptide hormones in sports, but it doesn鈥檛 yet have a test for growth hormone, let alone IGF-1. 鈥淚GF-1 is certainly on our radar screen, but there are quite a few things on the radar screen,鈥� says Donald Catlin, director of the Olympic Analytical Laboratory in the University of California at Los Angeles. Among them is albuterol, an antiasthma medication that has anabolic effects but which clears from the blood stream far more rapidly than steroids.

Growth hormone or IGF-1 are difficult to detect because they are peptides and unlike steroids are not readily excreted into urine. Officials are reluctant to move into blood tests, which would provide a better guide to abuse of growth hormone and IGF-1, because athletes object to this invasive approach. Another issue is deciding what levels of these compounds would indicate abuse. Natural levels of IGF-1 and growth hormone fluctuate throughout the day and vary from one individual to the next.

Officials admit that, given the ever more sophisticated pursuit of performance enhancing drugs, testing, even random testing, has limited effectiveness. But athletes know who the drug users are on their squad or within their sport, says Wade Exum, director of drug control and testing for the US Olympic Committee. 鈥淓ventually the athletes will start to expose the cheats.鈥�

Knuckleheads get cunning

BODYBUILDERS and weighlifters may be more interested in brawn than brain but they have come up with some cunning ways of diverting supplies of IGF-1 from the handful of medical research labs which manufacture it.

In one case, a lab technician at a Canadian university, seeking IGF-1 for his own bodybuilding programme, produced stationery with a false letterhead naming himself as head of the biology department. 鈥淲e thought this one was totally legitimate,鈥� says John Ballard, managing director of GroPep Proprietary, an Adelaide-based manufacturer of IGF-1. But the technician made the mistake of designating his home address for delivery. The courier company, expecting a university not a house, informed GroPep of the irregularity. Others try similar stunts. At the moment GroPep is receiving about five suspect calls per day, mainly from the US.

Things came to a head about a year ago when an Amercian distributor for GroPep filled an order for about 200 vials each containing about 100 micrograms of an IGF-1 analogue. Brand named 鈥淟ong R3鈥� IGF-1, it is thought to be about 10 times more potent than natural IGF-1 because of a chemical alteration that prevents it being mopped up by carrier proteins in the blood stream. The multi-vial shipment ended up in the hands of bodybuilders and accounts for most of the IGF-1 in use today.

Pictures of GroPep vials have even appeared in Muscle Media 2000 articles. Desperate to stop the trade, the company is now distributing IGF-1 directly to its customers. But Ballard admits there are still loopholes. Someone who registers a company simply to buy and divert IGF-1 would be difficult to stop, he says. And were the drug to go missing from research labs, 鈥渢hat would be impossible for us to catch鈥�.

Since GroPep wised up to their tricks bodybuilders have looked to other, perhaps more naive, companies for supplies of IGF-1. One target is Cephalon, a US biotechnology company that has recently reported success with clinical trials of IGF-1 in motor neurone disease. The company gets numerous suspicious calls despite the fact that it does not supply IGF-1 to a retail market. 鈥淭hey are certainly agressive,鈥� says John Farah, associate director of scientific affairs for the company. They call up with all sorts of lines, such as, they are high school science teachers doing experiments on cell growth and could they please have a free sample.

But when quizzed on the specifics of what IGF-1 is and what they plan to do with it, it becomes plain that 鈥渢hese are the knuckleheads鈥�.