Boxing is undeniably brutal’the goal is to knock out your opponent, the sooner the better. Films and novels have depicted the sad postboxing lives of many fighters. Some of the greatest champions of the ring have ended up broke and in poor health, despite having earned millions in their prime. It doesn’t happen only to the pugs without a punch, either.

Sugar Ray Robinson held the middleweight title of the world five times and won the welterweight title once. Considered by most boxing experts the best pound-for-pound fighter ever, Robinson was untouchable in his younger days. His punches came fast and hard, and by the time his opponent realized what hit him, Sugar Ray had danced away, often leaving his opponent lying on his back.

Financial pressures, however, made Sugar Ray stay in the ring too long. He was still fighting at 40 and began to lose to men who wouldn’t have lasted three rounds with him in his younger days. Ray took a lot of punches in those last fights, and the resulting head trauma may have contributed to the severe case of Alzheimer’s disease that eventually caused his death.

A more recent example of the effect boxing can have on the brain is Muhammad Ali, who may be the greatest heavyweight champion ever and who was voted second to Robinson in an Associated Press poll of the greatest boxers of the 20th century. Ali doesn’t have Alzheimer’s, but it’s clear from his slurred speech and slow gait that the once lightning-fast fighter is suffering. In his case it’s Parkinson’s; the brain cells that produce the neurotransmitter dopamine have been severely damaged.

Ali was born with an abnormally small pituitary gland, the area of the brain where dopamine is produced, and that area seems to have been selectively damaged by blows to the head. Of course, Ali didn’t realize that, and it certainly didn’t affect his earlier boxing skills. Like Robinson, however, Ali fought past his prime and consequently took many head punches that would never have landed in his younger days.

Traumatic brain injury can lead to severe damage to the pituitary gland. Located just behind the nose in the brain, the gland produces many vital hormones, including growth hormone, thyroid-stimulating hormone and gonadotropins such as luteinizing hormone, which controls testosterone synthesis.

Statistics show that more than 1.5 million Americans have suffered some form of TBI. Often it’s the result of head trauma, as from a violent car accident, but anything that violently hits the head can lead to TBI. About 40 percent of patients with moderate or severe head injury show damage to the pituitary gland. The hormones most affected by TBI are growth hormone and gonadotropins, the two primary anabolic hormones in the pituitary.

In some cases the damage is caused by direct injury to the pituitary gland. Or the damage may ensue from vascular injury, which limits blood flow to the gland, leading to the death of cells. A common cause of TBI is a concussion, an injury to the brain that often involves a temporary loss of consciousness and that has occurred in 40 percent of people diagnosed with TBI. The injury is common in contact sports, such as boxing, football and ice hockey. In fact, a boxer’s primary objective is to induce a concussion, which usually means knocking out the opponent.

No boxer walks away from the sport without suffering some form of brain injury. While a series of knockouts results in the greatest degree of brain damage, even being hit in the head repeatedly causes a shearing effect in the brain’because brain tissue is thrust violently against the skull’leading to an actual loss of brain cells. The cumulative effect can be devastating and may take years to show up. Early symptoms include slurred speech and slowed movement.

The worst aftermath of being hit in the head repeatedly, as in boxing, is a type of dementia that looks like Alzheimer’s disease: pugilistica dementia. Jerry Quarry, a great heavyweight of the ’70s who fought Ali, died from it, as have countless other fighters. All fighters know the risk of brain damage, and most try to end their ring careers before they lose their marbles. But a lesser known consequence of years spent in the ring has recently been recognized. Since boxing is a definite risk activity for the development of TBI and since TBI is known to lead to damage in the pituitary gland, researchers tested 11 recently retired or still competing boxers to check their growth hormone levels.1 ALL None of the boxers could be considered bums, since all were current or former world champions. Their average age was 38, with an age range of 18 to 55. None reported any serious illness, and none were taking any type of medication. But seven of the fighters complained of memory impairment, while another four complained about fatigue. None showed any symptoms that would suggest pituitary gland problems, such as a tendency to sleep, cold intolerance, low blood pressure, low blood glucose levels, reduced body hair, decreased sex drive, excessive urination and thirst.

Even so, 45.4 percent of the subjects had a growth hormone deficiency’rare in men that young. In another 36.4 percent the status of their growth hormone release was uncertain. Based on that finding, the authors suggest that GH deficiency is probably a common occurrence in boxers at all levels and occurs at a significantly younger age than it normally does.

Many readers are probably thinking that while this information is interesting (or maybe not), it doesn’t apply to them since they aren’t boxers. But consider the fact that any type of concussion, which always involves some brain injury, can damage the pituitary gland and result in a permanent loss of GH release. That could happen to an 18-year-old engaged in some form of martial arts, where head trauma results in a knockout. Or a car accident in which you get knocked out. That can injure the brain enough to cause pituitary trauma, either as a result of direct injury to the gland or through damage to the blood vessels that serve it.

Another aspect to consider is that the product of growth hormone, insulinlike growth hormone 1 (IGF-1), is known to be vital for the maintenance of neurons, the functioning cells of the brain. Recent studies show that GH itself exerts a protective effect on brain cells. A lack of adequate GH may promote brain degeneration.

Restoring Growth Hormone: A New Method?

Growth hormone and IGF-1, which is stimulated by GH, drop about 14 percent with each decade of life. By age 60 many people are deficient in GH, a condition that’s called ‘somatopause.’ Changes in the body that occur with a GH deficiency are typical of the physical decline associated with aging. They include a reduction in skeletal muscle mass and strength; increased bodyfat, especially in the abdominal area; an increase in low-density-lipoprotein cholesterol, which is the type most linked to cardiovascular disease; impaired blood clotting, which also predisposes them to heart attacks and strokes; increased blood pressure; reduced heart power; lowered immune re’sponse; and lower bone mass.

A lack of GH and IGF-1 is also associated with mental decline, including the loss of memory common with age. IGF-1 is involved in maintaining energy processes in the brain, the formation of new neurons, nerve stimulation reactions and other vital brain functions. Without GH and IGF-1 a toxic metabolite of the essential amino acid methionine, homocysteine, increases in the brain, resulting in further degenerative changes.

Knowledge that those adverse effects are linked to a deficiency of GH and IGF-1 has led to the concept of GH therapy. As a peptide hormone, GH must be injected. Another possible alternative treatment features the use of growth hormone secretagogues. When GH-replacement therapies are provided to people deficient in the hormone, the effects of GH deficiency diminish.

Providing GH therapy presents some formidable problems, however, starting with its high cost’potentially thousands of dollars. Since it’s not an officially accepted form of therapy, it isn’t covered by medical insurance. Side effects are also common, most often with higher-than-normal physiological replacement dosages: edema, or water retention, muscle pain and carpal tunnel syndrome, which pinches nerves in the wrists and hands. In addition, the long-term life-extension effects of GH remain speculative at best. Some scientists even suggest that long-term use of GH may shorten life span, though the evidence for that is sparse.

The reason GH declines with age has to do with the two hormones that control its release in the brain, growth-hormone-releasing hormone and somatostatin. GHRH promotes GH release, while somatostatin blocks it. With age somatostatin becomes dominant. The pituitary gland still continues to synthesize GH and exhibits no defects unless affected by trauma. That explains why drugs such as GH secretagogues work in older people; they bypass somatostatin. GH release is also affected by brain neurotransmitters, which are the chemicals that regulate nerve impulses in the brain. One neurotransmitter linked to GH release is acetylcholine, which is also linked to memory and learning functions. In Alzheimer’s disease, nerve cells that synthesize acetylcholine are destroyed, which results in the intellectual deficit characteristic of Alzheimer’s disease.

The present medical treatment of Alzheimer’s involves drugs that inhibit the primary enzyme that degrades acetylcholine in the brain. But since acetylcholine also promotes GH release, a group of researchers looked at whether the same drugs used to treat AD could also promote GH release.2 For eight weeks 24 older men were put on either a placebo or the drug donepezil, trade name Aricept, which is used to treat Alzheimer’s disease. They took a five-milligram dose for the first four weeks, 10 milligrams for the second.

There was a 53-percent increase in GH and a 31 percent increase in IGF-1 in the drug group. That change equals a shift to hormone levels typically seen in men 20 years younger, or about age 40. Still unclear is whether that level of GH increase would reverse some the negative effects seen with a GH deficiency. If this drug does work, it would dramatically reduce the current cost of GH therapy and also produce little or no side effects.

One point to consider is that the drug therapy would be useful only for those with a full-blown GH deficiency. For all others, using it would have little or no effect on GH release.

References

1 Kelestimur, F., et al. (2005). Boxing as a sport activity associated with isolated GH deficiency. J Endocrinol Invest. 27:RC28-RC32.
2 Obermayr, R.P., et al. (2004). The age-related downregulation of the growth hormone/insulinlike growth factor-1 axis in the elderly male is reversed considerably by donepezil, a drug for Alzheimer’s disease. Expr Geront. In press. IM

The amino acid L-arginine is most familiar today as the primary active ingredient in popular food supplements aimed at promoting the release of nitric oxide (NO). Arginine is the immediate nutritional precursor of, or raw material for, the body’s synthesis of nitric oxide. The reasoning behind such supplements is that NO is a potent dilator of blood vessels, and dilation can produce a greater degree of muscular pump during training’the muscle benefits through a heightened delivery of oxygen and nutrients.

But before arginine became linked to nitric oxide-boosting supplements, it was most associated with growth hormone release. While several other amino acids promote the release of growth hormone, arginine is particularly noted for that effect. In fact, an infusion of arginine at a dose ranging from 12 to 40 grams was often used to determine if a GH deficiency existed, especially in children.

The IV reliably promoted a release of GH in about 20 minutes, except in people deficient in the hormone. That information trickled down to the popular press, with books on longevity declaring that you could effectively promote GH release by taking arginine orally. Several studies appeared to confirm that assertion.

One such study involved 14 men, aged 15 to 30, who took 1.2 grams of arginine polyglutamate and 1.2 grams of L-lysine. That particular combination of amino acids promoted GH release five times greater than when either amino acid was used alone. Lysine and arginine normally compete for uptake in the body, since they both use the same amino acid transport system. Lysine is often suggested as a natural therapy for treating herpes infections because the virus requires arginine for growth and propagation. Lysine displaces arginine, thereby preventing viral replication.

Over the years other studies have attempted to test whether oral arginine is an effective GH releaser. No one questions the effectiveness of infused arginine. The problem with oral arginine is that there are a number of formidable barriers to its absorption, starting with the liver enzyme arginase, which degrades it. Another involves methylated arginine by-products of protein digestion that are inactive analogs of arginine but inhibit genuine arginine functions, including the synthesis of nitric oxide.

A few studies that concluded that oral arginine was ineffective for GH release suffered from flaws. One took only a single blood sample after an oral arginine dose, concluding that arginine showed no apparent GH release. Another was flawed because the researchers used too small a dose of arginine. The fear was that too large a dose would either be degraded in the liver or cause gastrointestinal distress. (Large doses of amino acids draw fluid into the intestine, which can result in nausea and vomiting.)

A new study, however, overcame most of the flaws of previous research and found some interesting results.1 Eight healthy men, aged 18 to 33, were examined on four separate occasions. The men reported to a lab after an overnight fast and were promptly fitted with a catheter in their forearm veins. Blood samples were taken every 10 minutes for five hours by the attending physician, Dr. Dracula (just kidding on that last one). A half hour after catheter insertion the men took doses of arginine in six ounces of water ranging from five to nine to 13 grams’or a placebo. Six drops of lemon juice disguised the considerable taste of the arginine (often described as being like dog vomit). The placebo had just the water and lemon juice.

The five- and nine-gram doses resulted in greater GH release than the placebo, but the 13-gram dose didn’t increase the release beyond that. In fact, the larger dose led to gastrointestinal distress. The GH rise occurred 30 minutes after the subjects took the arginine, compared to 20 minutes after an IV infusion. GH peaked after an hour.

Arginine primes the pituitary gland to induce the hypothalamus to release GH. It also suppresses the brain hormone somatostatin, which suppresses release of GH. Some scientists suggest that somatostatin release increases with age, explaining the drop in GH secretion that occurs in many older people.

The study showed that nine grams of arginine produced a GH release 45 percent greater than the five-gram dose, but that was considered statistically insignificant. More important, however, it showed that the pituitary gland can respond to oral doses of arginine.

The authors suggest that if you want a greater GH release during exercise, you should time your arginine dose with the start of your workout. Begin your workout 30 minutes after taking five to nine grams. They caution that some people don’t respond to any dose of arginine in relation to GH release. Taking a preworkout drink that contains protein or carb, which increases blood glucose, will likely blunt or prevent arginine-induced GH release. Keep in mind, too, that other amino acids compete with arginine for uptake into the body. So take arginine on an empty stomach.

1Collier, S.R., et al. (2005). Growth hormone responses to varying doses of oral arginine. Growth Horm IGF Res. In press. IM

Most oral anabolic steroids are merely molecularly tweaked forms of testosterone. They’re manipulated to concentrate the anabolic features of testosterone while minimizing its androgenic effects. Testosterone’s anabolic effects include increased muscle protein synthesis and mineral retention. The androgenic effects include male pattern baldness, acne and prostate gland stimulation.

The problem with taking straight testosterone orally is that nearly all the dose would be rapidly degraded in the liver and so would provide little or no anabolic activity. Oral anabolic steroids are designed to bypass the formidable liver metabolism that would otherwise occur. While oral steroids resist initial breakdown in the liver, however, they also tend to accumulate there because they aren’t rapidly degraded’and that can cause problems.

Oral-steroid accumulation in the liver leads to a swelling of liver tissues, an inflammation that’s a type of chemical hepatitis. ‘Hepatitis’ refers to any liver inflammation and can be caused by viruses, bacteria and drugs. The inflammation of the liver induced by oral steroids inhibits the circulation of bile that would normally be transported to the gallbladder for storage and release after a fatty meal is eaten. Bile helps reduce the size of fat particles and helps fat-degrading enzymes, or lipases, work more efficiently.

Cholestasis, the name given to any condition in which bile is blocked in the liver, produces jaundice, which is characterized by a yellowish skin tinge and a yellow tint in the whites of the eyes. Aside from jaundice, elevation in certain liver enzymes is the first indication that steroids are adversely affecting liver function. The condition could progress to a more serious disease, including a tissue breakdown that results in blood-filled cysts that, left untreated, could lead to liver failure.

Still, the worst-case-scenario of liver pathology rarely occurs with the majority of athletic anabolic steroid users. First of all, the liver can take considerable abuse’witness how long it takes the average alcoholic to die from liver complications. Second, most anabolic steroid users get off the drugs for a time to give their bodies a rest. That’s when the liver usually heals itself. The liver has remarkable regenerative capacity: You can remove two-thirds of it and still survive. Few organs in the human body can do that.

The medical literature reveals that nearly all cases of serious steroid-related liver complications occurred with hospitalized patients, who were often on the drugs continuously for five years or more. Even so, most steroid-using athletes realize that the liver is the organ that steroids hit hardest.

Over the years various substances have been touted as offering liver protection for oral-steroid users’antioxidants and gamma-linoleic acid derived from primrose or borage oils, for example. One substance that stands above all others in that regard is milk thistle.

Milk thistle has been known for thousands of years as a liver-protecting herbal. Its active ingredient is silymarin, which consists of three ingredients: silybin, silychristin and silydianin. They’re classified as flavonolignans, a type of flavonoid, and flavonoids are potent antioxidants. Silymarin appears to work best in the liver and kidneys. In the liver it improves liver cellular protein synthesis by stimulating DNA and RNA synthesis, which promotes cell regeneration. Silymarin also alters the outer membrane of liver cells, making them less permeable to toxic substances.

Another beneficial effect is that silymarin/milk thistle increases synthesis of a vital liver antioxidant called glutathione. Made from three amino acids, glutathione is one of the liver’s primary detoxifying elements, and its depletion signals imminent liver failure. That can happen if you’re foolish enough to eat a deadly mushroom called the amanita or dose up with more than six tablets of the active ingredient found in Tylenol. Administered in time, silymarin can save your life because it regenerates the glutathione that the toxins deplete.

Whether milk thistle can help protect the livers of those who use oral anabolic steroids was the subject of a study recently reported in a Serbian medical journal.1 Forty rats were divided into four groups. For eight weeks, five days a week, the first group was subjected to forced swimming and got the oral anabolic steroid Dianabol, two milligrams per kilogram of bodyweight. That would amount to 180 milligrams of Dianabol in a 200-pound man’a hefty dose by anyone’s standard. The second group got the same dose, underwent the same swimming test and, like the first group, got three times more food than their sedentary littermates. That group, however, also received silymarin in a dose of 20 milligrams per kilogram of bodyweight daily. The two other groups were control groups that did no exercise and got no drugs or supplements.

The rats in the first group showed indications of liver stress marked by an acute upgrade in the liver-repair process. The ones in the second group, on the silymarin, showed both increased glycogen deposition in the liver and upgraded glutathione activity, which appeared to block the steroid’s toxic effects on liver tissue. ALL You should be cautious in interpreting study results. While the research under discussion appears to confirm the protective effects of silymarin on liver function, the subjects were rats, not humans. As it happens, rat and human livers respond similarly to oral steroids. Since silymarin isn’t associated with significant side effects, it wouldn’t hurt a user of oral steroids to supplement with milk thistle standardized for 70 to 80 percent minimal silymarin content, up to 800 milligrams daily, in divided doses. Add to that turmeric, another herb that promotes bile flow and that may relieve the bile congestion that oral steroids bring to the liver.

Still, it would be a serious mistake to suppose that you can take oral steroids with impunity merely by supplementing with protective counternutrients. Silymarin may well offer some degree of liver protection, but it won’t overcome a lack of common sense.

Male Breast Cancer: Was Soy the Cause?

The use of soy food products remains a controversial issue. Soy proponents point to Asian people, who eat more soy-based foods than their Western counterparts and show lower rates of cancer and cardiovascular disease. Asian people also tend to be slimmer and eat more fish and less fat, which may account for the lower disease numbers. Nevertheless, studies have attributed health benefits to soy intake’less cardiovascular disease, less breast cancer in women, less prostate cancer in men and so on.

Now come the anti-soy advocates, saying that soy can interfere with thyroid hormone metabolism and testosterone synthesis. Among the active ingredients in soy are isoflavones, which are molecularly similar to estrogen. Known as phytoestrogens, meaning ‘plant estrogens,’ soy isoflavones may displace estrogen in the body, blunting its biological effects. Indeed, one recent study found that women who use soy products regularly are better protected against endometrial, or uterine, cancer, which is caused by excess estrogen.

In men small amounts of soy aren’t harmful and may help guard against prostate cancer and cardiovascular disease. When men use large amounts of soy foods or supplements, however, soy exerts estrogenic effects and may even lower testosterone levels.

To illustrate: A 58-year-old man reported to a local clinic because of gynecomastia, or male breast formation.2 The condition is common in bodybuilders who use large doses of certain anabolic steroids. Aromatase, an enzyme, converts the drugs to estrogen. Bodybuilders combat the effect with drugs that cripple the aromatization process.

The man who came to the clinic with gyno, however, wasn’t a bodybuilder’just concerned about maintaining his health. He’d been taking health supplements for the previous six years, including soy products; Salvia officinalis, also known as culinary sage, which contains phytoestrogens; and licorice root, which also lowers testosterone levels. He consumed two liters a day of salvia, with each liter containing 6,000 units of estriol, a form of estrogen. He took these supplements based on the advice of his wife, a pharmacist.

The doctors measured the man’s phytoestrogen level, finding it to be higher than that of Asian people who regularly eat soy products. They also found a localized mass in his chest that turned out to be ductal infiltrated carcinoma, a type of breast cancer.

Breast cancer in men, while on the rise, is still rare, accounting for less than 1 percent of all cases, and those mainly in patients aged 63 or older. The medical and family histories of the man at the clinic indicated no predisposition toward breast cancer. Nor was he fat, which is important because aromatase operates in peripheral fat stores; the fatter you are, the more aromatization takes place. His hormone profile at the time of his diagnosis, however, included a high estrogen level that would promote breast cancer under long-term conditions; it was at the upper limit for his age. He also had high levels of sex-hormone-binding globulin (SHBG) and low levels of total and free testosterone, as well as luteinizing hormone (LH), a pituitary hormone that controls testosterone synthesis in the testes.

Taking in large amounts of soy phytoestrogens suppresses LH release, which lowers testosterone synthesis in men. Phytoestrogens also increase SHBG, which ties up free testosterone, making the estrogen-to-testosterone imbalance even worse. In women phytoestrogens act as estrogen antagonists when estrogen is at a normal level, but when it’s low, as in older people, they can act as estrogen agonists, amplifying estrogenlike activity in the body. That explains why soy is believed to promote breast cancer in some women.

In the case described here, the man’s extensive phytoestrogen intake lowered his levels of androgens, which normally oppose the activity of estrogen and keep men from getting breast cancer. The phytoestrogens exerted full estrogen activity on his breast tissue, promoting cellular changes that led to cancer.

The case study patient unknowingly took in vast amounts of phytoestrogens and was lucky that the doctors who examined him found the breast cancer, since the disease tends to spread more rapidly in men and has shorter survival rates. The cancer had not spread to his lymph nodes, and he underwent a mastectomy to remove the primary tumor, followed by chemotherapy and radiation treatment. The researchers admit that they can’t definitively prove that the man’s extensive phytoestrogen consumption caused his breast cancer, yet when he stopped using the supplements, his hormonal balance returned. The take-home lesson from this plainly extreme example is not only that men should go easy on soy products but also that while a little bit of something may be beneficial, too much of a good thing can be dangerous.

References

1 (2003). Hepatoprotective effects of silymarin in patients with androgenic-anabolic steroid-induced liver damage. Med Pregl. 56 (Supp):79-83. (No authors listed)
2 Dimitrakakis, C., et al. (2004). Phytoestrogen supplementation: a case report of male breast cancer. Eur J Cancer Prevention. 13:481-484. IM

Here’s a quick quiz for you: What’s the most popular drug among bodybuilders? It isn’t any type of anabolic steroid or growth hormone, nor does it involve thyroid, beta agonists or any other anabolic substance. The most popular drug among bodybuilders is also the most popular drug world-wide: caffeine.

In the United States about four out of five Americans eat, drink or swallow a product that contains caffeine. Caffeine is ubiquitous in nature, existing in more than 60 known plants. About 75 percent of the caffeine consumed comes from coffee, with the other 25 percent mainly from tea and cocoa. Coffee, at an average 100 milligrams of caffeine per cup, contains twice as much caffeine as tea. A 12-ounce bottle of cola contains between 35 and 55 milligrams of caffeine.

Most people use caffeine to obtain benefits associated with it, including increased mental alertness, faster thought processes and reduced fatigue. Other effects’not specifically sought by most people’include stimulation of the heart, increased secretion of stomach acid and increased urine output.

Caffeine is thought to be an ergogenic aid in that it can enhance athletic performance. A study examined some of the fat-burning properties of caffeine under resting conditions and found that it increased energy expenditure 13 percent.1 Other effects included 24 percent increased fat oxidation, with 76 percent being recycled, likely due to the resting conditions in the study. Most of the effects were attributed to increased sympathetic nervous system activity, or the release of sympathetic hormones, such as epinephrine and norepinephrine, after the subjects took caffeine.

Caffeine-induced fatty acid release can interfere with insulin activity, leading to insulin insensitivity; however, research shows that exercise relieves that particular problem. Indeed, one recent study showed that drinking coffee offers protection against type 2 diabetes and suggested that nutrients besides caffeine, such as magnesium, may be the protective factors in coffee.2

Another recent study found that caffeine protects against Alzheimer’s disease by reducing the toxic effects of a protein called beta-amyloid on brain neurons3; buildup of beta-amyloid is considered a primary event in the onset of Alzheimer’s.

Since caffeine promotes the release of sympathetic hormones that stimulate body processes, it’s not surprising that it can induce severe anxiety in some people. Indeed, ‘caffeineism’ is so distressing that an estimated 20 percent of people cannot tolerate anything containing caffeine. One study, however, found that exercise can relieve anxiety brought on by high doses of caffeine.4

The release of sympathetic hormones by caffeine can stimulate the heart and increase blood pressure. Some drugs prescribed to treat cardiovascular disease, known as beta-blockers, block the effects of sympathetic hormones on the cardiovascular system. Caffeine would appear to be a problem because of the way it affects the cardiovascular system, but most studies have found no significant adverse effects except when excess intake is involved.

For example, one study examined the effects of caffeine on the body’s homocysteine levels.5 A toxic by-product of the metabolism of the essential amino acid methionine, homocysteine is linked to cardiovascular and other diseases. Healthy volunteers drank a liter a day of coffee for a month, and 24 of the 25 participants showed significant elevations of homocysteine in the blood. Vitamin B12, folic acid and vitamin B6 neutralize the effects of homocysteine, converting it into an innocuous substance that’s excreted from the body.

Another recent study found that drinking four cups of filtered coffee a day for one month increased cholesterol levels.6 Previous studies had shown that drinking unfiltered coffee increased cholesterol, an effect scientists traced to elements in coffee called diterpenes. Coffee filters captured the chemicals, making filtered coffee safe’or so they thought. Even so, the increase in cholesterol from coffee is significant only to those who already have elevated cholesterol. To others the effect is insignificant. ALL Drinking more than about five cups of coffee daily’particularly at night’can lead to insomnia. Besides caffeine coffee contains other substances, such as theophylline, a drug commonly used to treat bronchial asthma because it dilates the bronchial tubes. Coffee does that too. Another coffee ingredient, theobromine, was recently found to have cough-suppressant power superior to that in over-the-counter cough medications. Caffeine isn’t linked to any organ damage and peaks in the blood about two hours following ingestion. It’s metabolized by the liver, then excreted by the kidneys.

Coffee is believed to stimulate the brain by blocking brain receptors for a chemical called adenosine, which slows the activity of the brain’s working cells, or neurons. By blocking adenosine, caffeine fosters a feeling of mental clarity and focus. On the other hand, it also constricts blood vessels in the brain, which would decrease blood flow and lower metabolic activity.

Since caffeine is a drug, you might expect to pay a price if you quit cold turkey. The effects of withdrawal include headache, drowsiness and fatigue, mainly due to an increase in adenosine receptors in the brain.

As with other drugs, caffeine’s physiological effects depend on the dosage. The amount in an average cup of coffee’100 to 200 milligrams’leads to increased mental alertness and reduced fatigue. At the one-gram level symptoms of caffeineism, such as anxiety, mild heart-rhythm disturbances and gastrointestinal disturbances, appear. If for some crazy reason you were to ingest 10 grams of caffeine’the amount in 100 cups of coffee’at one time, you’d die.

Many of the popular so-called fat-burning supplements on the market contain some form of caffeine. Typical ingredients include guarana, an herb from Brazil that contains 7 percent caffeine’compared to the 2 percent found in coffee. A popular stimulant sold in the 1970s called Zoom was composed entirely of guarana, and its activity matched its name. Another form found in supplements is mate, also from South America.

The addition of caffeine to fat-burning supplements makes sense, since it promotes the release of sympathetic hormones, such as epinephrine and norepinephrine, which induce a biochemical cascade of fat from fat cells. The combination of ephedrine, which also promotes sympathetic-hormone release, and caffeine was considered the most effective natural fat-burning combination. Adverse publicity about ephedrine, however, eventually led to its being banned by the FDA. Could the fact that head-to-head comparisons found the ephedrine-and-caffeine combo to be superior to popular prescription diet pills have anything to do with the ban on ephedrine? You bet it could.

Caffeine was considered so ergogenic that the Olympics banned it above a certain quantity in the blood. The assumption was that the only way to reach that level of caffeine was to use it purposely as a means of improving performance. Some world-class cyclists were said to even use caffeine suppositories.

Caffeine is described as ergogenic because it releases greater amounts of fat in the blood, which spares limited glycogen stores in muscle. That helps increase muscular endurance, and studies involving endurance athletes have consistently proved boosting power of caffeine. The evidence for any effect on anaerobic exercise, such as bodybuilding, has been less clear. Recent studies, however, show that under anaerobic exercise conditions, caffeine ingestion appears to increase muscular endurance and decrease fatigue. An important point about these studies is that they all involved the use of pure caffeine, not food products containing caffeine, such as coffee. The effects of pure caffeine are considered more reliable. An Alternative to Pro-hormones?

In late October 2004, President George W. Bush signed the 2004 Anabolic Steroid Control Act, an amendment to earlier legislation that had made anabolic steroid distribution illegal. The new law covers nearly all over-the-counter pro-hormone supplements and discourages the development of new pro-hormone supplements designed to circumvent the new law.

An interesting aspect of the law is that few, if any, complaints about adverse health effects of pro-hormones had been reported to the Food and Drug Administration. The philosophy behind the new law is ‘protective’ because pro-hormone supplements are considered to be full-fledged anabolic steroids.

Companies were able to sell various pro-hormone formulas thanks to provisions in the Food Supplement Act of 1994, which diverted proof of danger of any particular supplement from the manufacturer to the FDA. The law also said that if a supplement existed naturally, it was by definition a food, not a drug, and therefore not subject to the stringent rules that affect drugs. The new law changes all that.

In fact, the recent banning of ephedrine for dubious reasons, plus the new mandate recently announced by the Federal Trade Commission to ‘vigorously pursue misleading claims in the supplement industry’ may spell the beginning of the end for many other supplements that the FDA will consider fraudulent or of dubious value to consumers. In essence, the agency is saying that most Americans are brain defective and cannot protect themselves, so the big brother FDA will do it for the poor fools. That, by the way, includes you and me.

Since pro-hormone supplements will be gone on January 23, 2005, we need to look at other ways of naturally increasing anabolic hormone levels. One way that is beyond the reach of even the FDA is movies. No, not porno movies, although they may be useful for other purposes. (I think I just gave away the fact that I didn’t vote for Bush.)

According to new research from the University of Michigan, watching certain movies can affect hormone levels in the body. Watching romance movies increases progesterone levels in women by 10 percent. When men watch such movies, their testosterone levels plummet.

Participants watched three different 30-minute film excerpts. The first was a romantic film called ‘The Bridges of Madison County.’ The next group watched ‘The Godfather, Part 2.’ The third group watched a documentary on the rain forest. All subjects had their hormone levels tested before, immediately before and 45 minutes following the films.

No changes occurred in the rain forest group. Women watching ‘Bridges’ showed a 10 percent rise in progesterone, with no change in testosterone. Men watching the same film showed lower testosterone levels. With ‘Godfather,’ which involved a violent scene, men showed a 30 percent rise in testosterone levels. Women with high testosterone levels showed a drop in that hormone while watching the scene, and those with low testosterone levels got ‘uncomfortable’ during the scene.

An implication of the study is that by inducing an elevated progesterone level in women, romantic films increase their feelings of affiliation to men. In men progesterone increases anxiety and has a blunting effect on testosterone. Which makes one consider that profound statement made by one Rodney King, whose 15 minutes of fame resulted from being at the epicenter of the incident that started the Los Angeles riots of 1991: ‘Can’t we all just get along?’

References

1 Acheson, K.J., et al. (2004). Metabolic effects of caffeine in humans: lipid oxidation or futile cycling? Am J Clin Nutr. 79:40-46.
2 Salazar-Martinez, E., et al. (2004). Coffee consumption and risk for type-2 diabetes mellitus. Ann Intern Med. 140:1-8.
3 Dall’lgna, O., et al. (2003). Neuroprotection by caffeine and adenosine A-2 receptor blockade of beta-Amyloid neurotoxicity. Brit J Pharm. 138:1207-09.
4 Youngstedt, S.D., et al. (1998). Acute exercise reduces caffeine-induced anxiogenesis. Med Sci Sports Exer. 30:740-45.
5 Urgert, R., et al. (2000). Heavy coffee consumption and plasma homocysteine: a randomized controlled trial on healthy volunteers. Am J Clin Nutr. 72:1107-10. 6 Strandhagen, E., et al. (2003). Filtered coffee raises serum cholesterol: results from a controlled study. Eur J Clin Nutr. 57:1164-68. IM

While a lot of research has pointed to undesirable side effects associated with anabolic steroid use, a good deal of it is flawed. Case studies, for instance, often examine the experiences of a few or even one person. They don’t prove much, since the adverse reactions of just a few people could be idiosyncratic, involving an individual sensitivity to the drugs used or a medical condition that became evident only after the drug use. Another problem is that researchers don’t work with realistic doses of the drugs in their studies. Scientists consider it unethical to administer the drug regimens used by many athletes today. They note that no published precedents prove the safety of such regimens, so using them constitutes bad medicine.

That’s led some scientists to observe athletes who get the drugs for themselves and use dosages and/or combinations that no doctor would advise. While risky from a health standpoint, such studies are nonetheless more realistic. Still, there’s no way to verify whether the doses and combinations reported by the athletes are accurate.

That leaves animal studies. The most obvious limitation of extrapolating animal research to human physiology is that humans may not react to drugs exactly as animals do.

In an effort to replicate real-world use of anabolic steroids by athletes, Japanese scientists gave massive doses of popular anabolic steroids to 37 rats that were divided into different groups.1 The first group got nandrolone decanoate, a popular injectable anabolic steroid with the trade name Deca-Durabolin; methenolone acetate, better known as Primobolan; and drostanolone, trade name Masteron. Group two got just Deca-Durabolin and saline, or salt, injections; group three, the control group got only saline injections.

All of the steroids were injected for six weeks. The medications were then stopped for four weeks and resumed for another six. Given the short life span of a rat, that is comparable to a few years for a human. The interesting part of the study was the dosages. The authors used a 132-pound reference human (people in Japan tend to be a bit smaller than in the West) and figured out doses that amounted to 100 times the suggested therapeutic ones. In order for the rats to to get the equivalent of the massive dose schedule used by athletes, that amount was extrapolated to the animals’ considerably smaller size. The authors believed that only that level of steroid use would produce pathological effects. The study yielded few surprises. As expected, the rats in the steroid groups showed higher levels of both testosterone and its by-product, dihydrotestosterone, than the control group. The drug rats also showed higher estrogen levels, likely from the high doses of Deca-Durabolin, 20 percent of which can convert into estrogen. The other drugs in the study were DHT-based and could not convert into estrogen.

The rodents’ organs showed severe damage to the hearts, testes and adrenal glands. The animals’ prostate glands showed enlargement but no evidence of cancer. In the testes, both Sertoli cells (where sperm cells are made) and Leydig cells (where testosterone is synthesized) were reduced in number. The animals’ natural secretion of testosterone was completely inhibited. Commenting on that, the authors noted, ‘Although students and athletes readily use anabolic steroid drugs, this finding is very shocking, and steroid users would most likely be quite alarmed if they knew of these pathological effects on the testes.’

That last observation shows how out of touch those researchers were with reality. Athletes have known of the hormone-suppressing effects of anabolic steroids for years. They attempt to counter the effects by using other drugs, such as estrogen blockers like Nolvadex or various aromatase blockers, which prevent the conversion of androgens into estrogens. Many also use HCG, an injectable drug with a structure similar to that of luteinizing hormone, the hormone that maintains testosterone synthesis.

In the section discussing how the steroid regimen in the rats led to inflammation in the heart, the authors suggest that former Olympic gold medal track star Florence ‘Flo-Jo’ Joyner may have died from cardiac complications of anabolic steroid use. Joyner’s official cause of death was related to a seizure.

The damage to the adrenal glands was explained by the presence of androgen receptors there. The authors think that some kind of hormonal negative-feedback mechanism may have caused the adrenal damage. But what about giving the animals dosages equivalent to 100 times the therapeutic dose based on weight? Wouldn’t that impose enough stress on the rodents to burn out their adrenal glands?

A major problem with the study is the doses used. They are excessive. An example is the dose used for Deca-Durabolin. The authors think that some athletes are injecting 20,000 milligrams of Deca? Heck, even with a drug that has the reputation of being relatively mild, such as Deca, that would be a near-fatal dose. ALL Does that mean the steroid regimens used by athletes and bodybuilders are safe? Unlikely. While athletes may not use doses comparable to those given to the rats in this study, they do use a lot more than what would ever be used therapeutically

Excessive Bodyfat: A Growth Hormone Deficiency?

Most people are fat because they eat too much and exercise too little. They don’t burn enough calories through their daily activity. That’s the simple equation of obesity, but as scientific discovery marches on, the body-composition equation becomes increasingly complex.

An example is the success of low-carbohydrate dieting. Many recent studies that have compared low-carb to other types of diets, such as lowfat, show that low-carb diets work better for most obese people. That’s true even when the competing diets contain an equal number of daily calories and a similar level of physical activity among study subjects.

The usual explanation for the apparent superiority of low-carb diets relates to hormones. A primary objective of low-carb dieting is insulin control. Most people with excess bodyfat levels oversecrete insulin, a storage hormone that works mainly to help store bodyfat. Thus, by limiting carbohydrates, the food element that promotes the greatest release of insulin, obese people are able to tap into and oxidize excess fat stores. Other hormones also play prominent roles in body composition. Thyroid hormone controls basal, or resting, metabolic rate, so a person’s thyroid gland must be functioning optimally to promote fat loss. On the other hand, taking excessive doses of pharmaceutical forms of thyroid hormone can have a pronounced catabolic effect in lean tissue. Most obese people have normal thyroid function, and the body responds to a drastic reduction in calories by lowering active thyroid output as a means of preserving vital tissue. Known as the dieting plateau, the effect can be overcome in many cases with small doses of thyroid hormone. That should always be medically supervised to avoid side effects.

Growth hormone has a reputation as a fat burner, which explains the plethora of GH-promoting food supplements that are touted as helping lower bodyfat. Whether it’s of any use in treating obesity or lowering bodyfat is a subject of contention among scientists. On the other hand, people who are deficient in GH always show significant body-composition improvement when given the hormone, including decreased bodyfat and increased lean mass.

The problem with using growth hormone as a fat-loss therapy involves not only the considerable expense of the drug itself, as well as the availability, but also possible side effects. When people are given amounts of GH greater than the doses used to treat GH deficiency, they commonly experience side effects, including edema, or water retention. Edema occurs because GH promotes the release of aldosterone, an adrenal hormone that retains sodium and water in the body. Joint pain, another common side effect, is likely related to GH’s influence on connective-tissue growth. Excessive connective-tissue growth leads to effects such as carpal tunnel syndrome, a painful nerve impingement at the wrist that may require surgical correction. In other cases GH is associated with hypertension and glucose intolerance, even gynecomastia, a condition of excess glandular tissue in male breasts.

A kind of GH that exists only in experimental form appears to offer the fat-lowering effects of growth hormone without the side effects. It won’t be available for many years, however. In the meantime, is there a dose that will effectively lower bodyfat without side effects?

According to a recent double-blind study, there is.2 Fifty-nine obese men and women were randomly assigned to either a GH group or a placebo group. The study lasted six months, and the subjects initially injected themselves with either 200 micrograms of GH or a placebo. After a month the dose was increased to 400 micrograms for men and 600 for women. The women got more because women are less sensitive to GH than men. After that, all groups got off the GH, and the researchers followed them for another three months.

Those in the GH group lost 2.4 kilograms’a modest amount, but it was composed entirely of bodyfat. They lost no lean tissue, or muscle, at all. That’s consistent with the known effects of GH: maintaining lean mass while promoting use of fat as a fuel source. Precisely how the GH promoted the fat loss isn’t known.

None of the usual side effects linked to GH showed up in any of the subjects, an effect attributed to the low doses used in the study. Those using the real GH did show normalized levels of IGF-1, a product of GH release produced in the liver. The GH group also had a 19 percent increase in high-density lipoprotein, a cardiac- protective cholesterol carrier in the blood.

The authors suggest that in people who have excessive bodyfat, lower GH and IGF-1 levels may help perpetuate obesity. Adding small doses of GH to compensate for the apparent deficiency could promote a selective loss of bodyfat while preserving or promoting a gain in lean tissue that would help increase resting metabolic rate, thus maintaining lower bodyfat levels.

References
1 Takahashi, M., et al. (2004). Endocrinological and pathological effects of anabolic-androgenic steroid in male rats. Endocrine Journal. 51:425-34.
2 Albert, S.G., et al. (2004). Low-dose recombinant human growth hormone as adjuvant therapy to lifestyle modifications in the management of obesity. J Clin Endocrinol Metab. 89:695-701. IM

Nandrolone decanoate is an injectable anabolic steroid marketed under various trade names around the world, the most familiar being Deca-Durabolin, or simply Deca. It’s popular for bodybuilding purposes for a number of reasons. While it has significant anabolic effects, most of the androgenic effects linked to testosterone use’such as acne and male-pattern baldness’don’t occur as readily with Deca.

When Deca is exposed to the enzyme 5-alpha reductase, which converts testosterone into dihydrotestosterone (DHT), the resulting metabolite is dihydronandrolone, which exerts far weaker androgenic force than DHT. While testosterone is subject to conversion by another enzyme, aromatase, into estrogen, that occurs with only about 20 percent of administered Deca, so users are able to avoid many of the side effects linked to estrogen, such as gynecomastia and water retention.

The consensus among bodybuilders is that Deca doesn’t offer the same bang as testosterone but is safer in the long run. If Deca does have a drawback, it relates to mild progesterone activity, which can cause effects similar to elevated estrogen levels in men. That would likely occur only with high doses, such as 600 milligrams or more a week.

The other major problem is that it’s notorious for being the most easily detected steroid in drug testing. Deca can leave traces in the body detectable even a year after use. As the sports pages reveal, most of the drug busts occurring in athletics today result from some form of Deca, including over-the-counter 19-nortestosterone-based pro-hormone supplements, which produce metabolites similar to Deca’s.

One persistent question about Deca and other anabolic steroids is whether the gains they produce consist of muscle, water or a combination. A new study examined the issue of body-composition change.1 The subjects were 16 experienced bodybuilders, nine of whom received weekly intramuscular injections of 200 milligrams of Deca for eight weeks. The other seven received a placebo.

Unlike previous studies, this one used four different body-composition tests. Its objectives were to determine the precise nature of gains made on Deca, to separate gains in muscle from those of water, and to note any changes in bodyfat content. It represents the most concise method ever devised for measuring actual gains after steroid use.

After eight weeks those in the Deca group showed significant gains in fat-free mass and total body water but no changes in extracellular water content, bodyfat or bone density. The authors concluded that all the gains consisted of pure muscle.

Growth Hormone and Testosterone: Anabolic Partners

Human growth hormone and testosterone injections are thought to be de rigueur for bodybuilders wanting the monstrous look of today’s professional competitors. The question of why that particular combination appears to work so effectively isn’t often answered, however. The prevailing notion is that taking the two drugs offers some sort of synergy.

A new study describes how testosterone and growth hormone interact in men.2 Growth hormone, like other hormones, has a feedback mechanism. When the body secretes a certain level of GH, other hormones in the brain are released that turn off the GH faucet. That’s termed ‘autonegative feedback.’ One theory about the relationship between testosterone and GH is that test may relieve GH feedback.

To test the theory, 13 healthy men, aged 43 to 71, received three weekly injections of either 200 milligrams of testosterone enanthate or a placebo. They also got growth hormone and GH-releasing peptide to blunt resting GH release via autonegative feedback. When taken without testosterone, the GH and GH-releasing peptide blunted resting GH release as expected. But in the subjects who were also getting testosterone, resting GH release returned to normal, and the feedback inhibition was relieved.

Exactly how the testosterone accomplished that isn’t clear, but the authors note that since the major inhibitor of GH release is another hormone called somatostatin, testosterone may have blunted somatostatin release. In addition, test may promote the release of growth hormone-releasing hormone from the brain’s hypothalamus. Both events would increase GH release. ALL More Than You Bargained For

Studies reported in this column show that some nutritional supplements contain additives that don’t appear on the label. An example of this is a popular ‘fat-burner’ supplement that analysis revealed contained a few pro-hormone ingredients. The latest study of pro-hormone contamination has an international flavor, since it focused on supplements sold in various countries around the world.3

Researchers purchased 634 supplements in 13 countries from 215 different suppliers, making this study the most extensive look at the pro-hormone supplement business ever published. Ninety-four, or 14.8 percent of the sample, contained pro-hormones not listed on the label. The supplements came from five countries: the USA, Netherlands, United Kingdom, Italy and Germany. They included 316 capsules, 231 tablets, 72 powders and 15 fluids.

Of the supplements that tested positive, 23 contained nandrolone and testosterone, 64 contained only testosterone, and seven contained nandrolone only. The authors believe that the anabolic steroids found in the supplements weren’t intentionally added but likely resulted from cross-contamination. That implies poor quality control. Vats used to make pro-hormones are later used for other supplements, and pro-hormone residue gets passed into the second supplement.

About 10.6 percent of the nonhormonal supplements contained testosterone, which isn’t legal for over-the-counter sales. How did testosterone get into the supplements? Some may have been produced during pro-hormone processing but not removed from the supplement. True, oral testosterone is deactivated by the liver and thus has no anabolic effects in the body. Oral anabolic steroids, however, are modified to prevent liver breakdown.

Pro-hormone levels in these supplements aren’t likely to have any effect, since they appear in low concentration and would also be mostly degraded during first-pass metabolism in the liver. A few of the analyzed supplements, however, contained enough nandrolone metabolites to produce a positive drug test. That may explain the recent plethora of nandrolone drug busts in athletics. Athletes may not be aware that some supplements may be high enough in nandrolone to produce a positive result.

Aromatase Blockers: Natural and Synthetic

Aromatase is a ubiquitous enzyme existing in the brain, muscles and fat. Its primary function is to convert androgens into estrogens. Specifically, aromatase converts androstenedione, an adrenal androgen, into estrone, a weak form of estrogen. Aromatase also converts testosterone into estradiol, the most potent of estrogen’s three forms.

One-third of the estrogen synthesized in women’s bodies is produced during the conversion of androstenedione into estradiol. Some forms of breast cancer depend on estrogen stimulation, and drugs to decrease estrogen production are often used to treat the disease. Of the new drugs, the aromatase inhibitors are becoming increasingly popular in therapy.

Being able to control estrogen is important to male bodybuilders because many popular anabolic steroids, such as testosterone, are subject to aromatization. That means elevated estrogen, leading to excessive water retention, increased subcutaneous bodyfat and excessive male breast tissue, or gynecomastia.

When faced with an overabundance of estrogen, athletes often resort to using either estrogen-receptor-blocking drugs, such as Nolvadex, or aromatase blockers, such as Arimidex or Aromasin. They prefer aromatase-blocking drugs for a number of reasons. Estrogen-receptor blockers don’t directly inhibit estrogen synthesis; they only compete with estrogen to gain access to cellular estrogen receptors. Drugs such as Nolvadex show weak estrogenic activity, and with high doses or long-term use they can have a paradoxical effect, acting themselves like estrogen. Other studies show that Nolvadex can block enzymes in the testes required for testosterone synthesis.

Several years ago a natural aromatase blocker, originally called Flavone X, was touted as a potent aromatase blocker. Flavone X was later identified as chrysin, a natural flavonoid found in honey and bee propolis. People were excited about chrysin because research proved it to be the most potent natural aromatase inhibitor yet found, comparable to drugs such as Cytadren. Well, those studies used in vitro, or isolated-cell, study designs. Subsequent experiments found that chrysin had poor bioavailability, being mostly metabolized in the intestines, then excreted. That was confirmed in a recent study, in which 20 healthy men, aged 25 to 30, ate quantities of honey and propolis equal to suggested supplemental amounts of chrysin for 21 days.4 Their testosterone levels didn’t change.

Although officially used as a treatment for breast cancer in older women, aromatase-inhibitor drugs will likely be used for other purposes, all related to estrogen, in the near future. Bodybuilders and other athletes are already using them in conjunction with anabolic steroids as a means of controlling the estrogen that would otherwise result from high-androgen drug regimens.

Besides, aromatase blockers may be useful in treating low testosterone levels in older men.5 That condition, sometimes called andropause, is linked to several health problems, such as cardiovascular disease, Alzheimer’s disease and lean-tissue loss. Andropause treatment is controversial, since the various forms of testosterone that serve as the primary treatment all have problems.

The impact of testosterone injections peaks in about two weeks, then drops precipitously. Excess test is linked to lower levels of high-density-lipoprotein (HDL) cholesterol, which offers protection against cardiovascular disease. Physicians also worry about other side effects of testosterone-replacement therapy, such as excessive red-blood-cell production, which can increase the viscosity, or thickness, of the blood, a scenario that favors strokes. Another possible problem is stimulating prostate cancer, although that isn’t actually caused by testosterone but in genetically predisposed men rather results from stimulation of the prostate by dihydrotestosterone (DHT) and estrogen.

In the new study only one milligram of Arimidex a day for 12 weeks increased testosterone levels in the aging men to a level similar to that found in teenagers. The drug also increased luteinizing-hormone release from the pituitary gland (which controls testosterone synthesis in men) and decreased estrogen levels. In older men, aromatase becomes more active, likely the result of bodyfat accretion, and leads to an imbalance of the kind that happens to steroid-using bodybuilders. The success of Arimidex suggests that it may be an effective way to treat low testosterone levels without major side effects.

At the other end of the aging spectrum, new research shows that aromatase blockers may promote growth in short children. Estrogen limits growth by promoting the sealing of the ends of bones. Once that happens, all longitudinal, or height, increases end. Blocking the effects of estrogen may increase height in short children.

A recent study tested the usefulness of a new aromatase-inhibiting drug, Aromasin, or exemestane, in young men aged 14 to 26.6 Subjects received doses of either 25 or 50 milligrams of Aromasin daily for 10 days. The 25-milligram dose suppressed estrogen by 38 percent, while the 50-milligram dose suppressed it by 32 percent. Testosterone levels increased 60 percent and 56 percent. The drug peaked in the blood about an hour after ingestion, with a half-life, or half the time it takes to eliminate the original dose, of 8.9 hours. Peak estrogen suppression occurred at the 12-hour mark.

A guide to anabolic drug use states that Aromasin blocks ‘an average of 85 percent of estrogen,’ but that figure represents the activity of the drug in older women. The figures of 32 percent or 38 percent are more relevant for bodybuilders.

References

1 Wouter, D., et al. (2004). Bodybuilders’ body composition: effect of nandrolone decanoate. Med Sci Sports Exer. 36:484-489.
2 Veldhuis, J.D., et al. (2004). Short-term testosterone supplementation relieves growth hormone autonegative feedback in men. J Clin Endocrinol Metab. 89:1285-1290.
3 Geyner, H., et al. (2004). Analysis of nonhormonal nutritional supplements for anabolic-androgenic steroids’results of an international study. Int J Sports Med. 25:124-129.
4 Gambelunghe, C., et al. (2003). Effects of chrysin on urinary testosterone levels in human males. J Medicinal Food. 6:387-90.
5 Leder, B.Z., et al. (2004). Effects of aromatase inhibition in elderly men with low or borderline-low serum testosterone levels. J Clin Endocrin Metab. 89:1174-1180. 6 Mauras, N., et al. (2003). Pharmacokinetics and dose finding of a potent aromatase inhibitor, Aromasin (exemestane), in young males. J Clin Endocrinol Metab. 88:5951-5956. IM

Losing bodyfat is easy: All you have to do is burn more calories than you eat, increasing your exercise and decreasing your total daily calorie intake. By reducing your current diet by 500 calories a day, you’ll lose one pound of fat each week, guaranteed. But as anyone who’s ever dieted knows, losing bodyfat just isn’t that simple.

Once you reach a certain bodyweight, your body establishes that as your norm and vigorously opposes any attempt to change your set point, resisting changes in composition by slowing your metabolism and increasing your hunger sensations. That’s why any attempt to lose a significant level of bodyfat turns into a matter of will’literally you against yourself. No wonder most diets fail. Another common scenario occurs when you diet and exercise steadfastly and lose weight, only to see the fat return with a vengeance when the diet ends.

So most people need help losing bodyfat’something to keep the fat-burning process at maximum capacity while diminishing the incessant food cravings that doom most diets. Several food supplements have been touted as meeting those goals. The most prominent and generally the most effective are so-called thermogenic agents. The word thermogenic refers to the activity of what scientists call ‘futile energy cycles,’ whereby calories convert into heat instead of being stored as fat.

Ephedrine and its native natural herbal source, mahuang, have been the thermogenic supplements of choice in recent years. Many published studies attest to the effectiveness of ephedrine-based food supplements for fat-loss purposes, but that’s also spelled their commercial doom. Reports of health problems related to ephedrine-based supplements are common these days, though such products have been used without problems for nearly a century. What really seems to be going on is that casting suspicion on ephedrine’s safety is in the best commercial interests of some industries’notably pharmaceuticals manufacturing.

Unfounded reports about the alleged dangers of ephedrine are often based on the experiences of people who either had no business using the supplements in the first place due to medical contraindications or had occult health problems that ephedrine aggravated. The fact is, untold numbers of people have used ephedrine daily, with no side effects besides the significant fat loss they experienced.

Nevertheless, ephedrine’s days appear to be numbered. Already, a few states have banned the sale of ephedrine and mahuang. Fearful of litigation, supplement companies have removed the substances from their thermogenic fat-loss formulas, replacing them with ingredients that are so ineffective that they perform little better than a placebo. The market for fat-loss supplements is so huge, however, that companies are loath to forgo the fat-loss cash cow.

Fat-loss supplements commonly contain two ingredients: hydroxycitrate (HCA) and chitosan. Now that ephedrine must relinquish its throne as king of the fat-loss supplements, the salient question becomes whether such ingredients as HCA and chitosan actually promote fat loss. Let’s take a look at the HCA evidence.

Hydroxycitrate Acid

HCA is extracted from the rind of a fruit common in Asia and India. It’s the principal acid found in the brindleberry, also known as Garcinia cambogia, making up 16 percent of the weight of the dried fruit. HCA works by inhibiting an enzyme called ATP citrate lyase, which controls the conversion of citrate and coenzyme A into oxaloacetate and acetyl coenzyme A, an ingredient in the synthesis of acetylcholine in the brain and in the synthesis of fatty acids, cholesterol and triglycerides elsewhere in the body. By suppressing the synthesis of acetyl coenzyme A, HCA may suppress fat synthesis.

Scientists also think that HCA prevents the conversion of carbohydrates into bodyfat, instead shifting excess carbs toward the metabolic pathway of glycogen formation in muscle and the liver. One theory of appetite suppression is that when liver glycogen stores are full, appetite is suppressed, which implies that HCA also functions as an appetite suppressant.

Particularly in the case of a carb-rich diet, acetyl coenzyme A may take another metabolic pathway that leads to production of a substance called malonyl coenzyme A (MCA). The problem with malonyl coenzyme A is that it blocks the activity of enzymes that work with carnitine in shuttling fat into the mitochondria of cells, where fat oxidation occurs. So inhibiting the activity of malonyl coenzyme A’as HCA supposedly does’would lead to greater fat oxidation during exercise. ALL It’s hard to overstate the fact that the primary enzyme HCA inhibits, ATP citrate lyase, is most active in high-carbohydrate diets. In fact, there’s some evidence that using HCA-based supplements during low-carbohydrate dieting is ineffective. High-carb diets always elevate the activity of ATP citrate lyase, making fat synthesis more likely.

A number of studies have examined HCA’s link to fat loss. Their findings have been equivocal at best. Some studies show that HCA extends definite beneficial effects, and others show few or no benefits. Many of the studies, however, have been influenced by such other factors as exercise and the nutrient composition of the diet.

In a study published two years ago, 24 overweight men and women took 900 milligrams of either a placebo or HCA for six weeks.1 After two weeks energy intake decreased by 15 to 30 percent in the HCA group, chiefly between meals. The authors suggest that HCA may be more effective at preventing weight regain due to its appetite-suppressing properties.

An earlier double-blind, placebo-controlled, randomized study, however, came to a different conclusion.2 For three days subjects took three grams of HCA or a placebo, and researchers examined the effects of exercise with and without HCA use. They found no differences in fat oxidation between the placebo and HCA. Nor did HCA affect energy expenditure, either at rest or during exercise.

The authors suggest that perhaps the HCA dose was too low and the three-day experiment too short for them to adequately gauge HCA activity. Another problem: The study subjects were on a typical American diet containing 35 percent fat, but the authors didn’t mention the diet’s carb content, even though HCA’s main function is to prevent conversion of excess carbs into fat.

A study presented at the 2002 Experimental Biology meeting that compared HCA to a placebo suggests that HCA may modulate obesity genes. The subjects took the HCA or a placebo 30 minutes before meals, and both groups took in the same number of daily calories’2,000. They also participated in a walking exercise program. At the end of eight weeks the HCA group showed a 4.8 percent loss in bodyweight and a 40 percent decline in plasma leptin levels.

In another study, scientists combined HCA with another popular supplement aimed at fat loss, medium-chain triglyceride, or MCT.3 For two weeks the subjects took either 500 milligrams of HCA alone or the same dose with three grams of MCT. Another group took nothing. All groups showed significant bodyweight loss, and there was no significant difference between the groups. Those in the supplement group showed no more evidence of increased energy expenditure, fat oxidation or satiety than the placebo group. Because the subjects were in a negative energy balance, however, no fat would be synthesized, and HCA wouldn’t be expected to do anything.

In analysis consistent with other research, the authors suggest that HCA would be more likely to prevent weight regain following a diet than to burn fat during one because it works by preventing excess calories from becoming fat. People who are dieting rarely get too many calories. As for those who do eat large amounts of carbs and then engage in endurance training, the question remains whether HCA intake would lead to greater fat oxidation.

In a study of endurance athletes subjects got either 250 milligrams of HCA or a placebo for five days, then did a cycling routine for an hour at 60 percent of maximum oxygen intake, followed by a routine that increased the pace to 80 percent of maximum oxygen intake, until exhaustion.4 The HCA group showed increased fat oxidation and lowered carb oxidation during exercise.

In another study that featured a two-hour cycling routine, however, HCA did nothing, even though the cyclist subjects got six to 30 times more HCA than the subjects of previous studies.5 No changes occurred in either fat or carb oxidation during exercise. Evaluating HCA Research

HCA research shows equivocal results because of other factors that may affect how it works. In particular, HCA seems to do little or nothing for those on a low-calorie or low-carb diet, but it may be of some help in preventing weight regain after a diet, when you have a greater chance of taking in excess carbs or calories. HCA may also work on low-carb-diet ‘cheat days,’ when it would divert carbs away from storage and toward glycogen replenishment in muscle and the liver.

Safety concerns about HCA aren’t a major problem. It doesn’t promote catecholamine release, as ephedrine does, so there are no cardiovascular complications to worry about. On the other hand, by limiting the synthesis of acetyl coenzyme A, HCA may also slightly inhibit the synthesis of acetylcholine, a brain neurotransmitter involved in learning and memory. Alzheimer’s disease is marked by a drop of acetylcholine levels in the brain, and people with memory problems should exercise caution before taking large doses of HCA.

By inhibiting acetyl coenzyme A, the starting point for cholesterol and steroid hormones, HCA could also, in theory, interfere with hormone synthesis. According to researchers, however, that should be of concern only to pregnant or breast-feeding women.6

Another substance HCA inhibits, malonyl coenzyme A, not only prevents fat-burning but also helps transmit the insulin signal to cells. So by inhibiting MCA production, HCA could foster insulin insensitivity. That’s never occurred with typical supplement doses, but diabetics should exercise caution with HCA all the same.

HCA works best when taken 30 to 60 minutes before meals and when taken in divided doses of 750 to 1,500 milligrams daily. Avoid HCA lactone supplements, which have zero activity in humans.

References

1 Westerterp, M.S., et al. (2002). The effect of hydroxycitrate on energy intake and satiety in overweight humans. Int J Obesity. 26:870-872.
2 Kriketos, A.D., et al. (1999). Hydroxycitric acid does not affect energy expenditure and substrate oxidation in adult males in a postabsorptive state. Int J Obesity. 23:867-873.
3 Kovacs, E.M.R., et al. (2001). The effects of two-week ingestion of hydroxycitrate and hydroxycitrate combined with medium-chain triglycerides on satiety, fat oxidation, energy expenditure and bodyweight. Int J Obesity. 25:1087-1094.
4 Lim, K., et al. (2002). Short-term hydroxycitrate ingestion increases fat oxidation during exercise in athletes. J Nutr Sci Vitaminol. 48:128-133.
5 Van Loon, J.C,. et al. (2000). Effects of acute hydroxycitrate supplementation on substrate metabolism at rest and during exercise in humans. Am J Clin Nutr. 72:1445-1450.
6 Jena, B.S., et al. (2002). Chemistry and biochemistry of hydroxycitrate acid from Garcinia. J Agric Food Chem. 50:10-22. IM

According to existing research, the most adverse effects of using anabolic steroids occur in the cardiovascular system. These problems mostly arise with oral anabolic steroids, many of which unfavorably alter blood lipid, or fat, profiles. The good research news is that when steroid use stops, blood lipid levels return to normal. So those who never get off steroids are at a higher risk for serious cardiovascular problems, including heart attacks and strokes.

Oral anabolic steroids tend to speed up the liver degradation of high-density lipoprotein (HDL), a protective cholesterol carrier in the blood. On the other hand, several other studies show that steroids may lower levels of lipoprotein(a), a substance that acts similarly to low-density lipoprotein (LDL) in promoting cardiovascular disease. Conversely, growth hormone raises levels of lipoprotein(a).

The notion that these adverse cardiovascular effects are reversed when someone stops using steroids is based on short-term studies, usually lasting no longer than three to six months. What happens after that is still a matter of debate. Researchers from the University of Glamorgan in the United Kingdom presented a study at the 2002 meeting of the American College of Sports Medicine in St. Louis that examined the long-term use of steroids and their effects on certain indicators of cardiovascular health.

The 32 subjects in the study were age matched and divided into four groups:

1) Steroid users still on the drugs
2) Steroid users off the drugs at least three months
3) Drug-free bodybuilders
4) Sedentary controls

The steroid groups included men who had used the drugs for more than 20 years, though not necessarily consistently. As expected, both groups had higher levels of body mass, while the sedentary group had the highest bodyfat levels. Those still using steroids had higher LDL levels and lower HDL levels, a scenario typical of oral anabolic steroid drugs.

The surprising finding of the study was that both steroid groups showed elevated lipoprotein(a) levels. In the steroid group that had abstained from using the drugs for at least three months, HDL and LDL levels had returned to normal, but lipoprotein(a) levels remained elevated, which doesn’t bode well for the subjects’ future cardiovascular health. As to why the steroids elevated lipoprotein(a) when previous studies showed a lowering effect, the authors would not hazard a guess. If other studies confirm that finding, it may mean that long-term steroid use may permanently alter blood lipid levels, especially lipoprotein(a).

Mahuang vs. Ephedrine

The government appears to be more interested in removing synthetic ephedrine from the market than mahuang, the natural source of ephedrine. While the ostensible reason is that synthetic ephedrine is more dangerous, the actual reason is that some people have used ephedrine as a base in the production of illicit amphetamines. But is there a difference in the way mahaung and synthetic ephedrine are metabolized in the body? Determining that was the goal of a study presented at the 2002 meeting of the American College of Sports Medicine. The study consisted of six subjects, all over age 21: Half of them received mahaung standardized to contain 20 milligrams of ephedrine, while the other half received 20 milligrams of pure synthetic ephedrine.

After taking the mahaung or ephedrine, the subjects provided blood samples at the three, six, nine and 12-hour mark. The blood concentration of ephedra in both groups was similar by the third hour. After that, however, blood concentrations from the mahaung group dropped until the sixth hour, then rose again by the ninth hour, reaching a higher level than the synthetic ephedrine.

The results show that mahaung and pure ephedrine are not metabolized in the same way. Extended effects may occur when using mahaung.

Is Tribulus an Aphrodisiac?

Tribulus terrestris, also known as puncture vine and caltrop fruit, is an herbal supplement touted as a natural anabolic. That reputation is based on poorly conducted studies from the old Eastern bloc nations, such as Bulgaria, that showed tribulus apparently increasing testosterone levels by promoting the release of luteinizing hormone (LH), a pituitary hormone that controls testosterone synthesis in the testes. A 1997 study showed that tribulus appeared to help treat male infertility, leading to the idea that it may also possess aphrodisiac properties. ALL In fact, animal studies do show such sex-stimulating effects. In a study involving white rabbits published in 2000, tribulus promoted erections in the bunnies. But then again, what wouldn’t promote sexual activity in rabbits? The same researchers decided to examine the effects of tribulus on groups of castrated and uncastrated rats to see what sex-promoting effects it provided compared to testosterone cypionate, known to promote increased libido.1

Castrated rats were used because from a sexual-activity standpoint, you can’t get lower than that. Other groups included both normal and castrated rats given only saline solutions as a placebo for control purposes. The study showed that while testosterone promoted the greatest increase in sexual behavior in both normal and castrated rats, tribulus offered only slightly less potent benefits.

Previous studies involving human and animal subjects pointed to an ingredient in tribulus called protodioscin (PTN), which is a saponin with a structure similar to that of active steroids, such as DHEA. According to the study authors, PTN as a component of tribulus may increase sexual activity by influencing DHEA behavior. In animals and human females DHEA reliably converts into testosterone; however, in human males it usually converts into androstenedione, then estrogen.

Does that mean that in humans tribulus is more likely to have an aphrodisiac effect in women? That idea hasn’t been tested, but many men who’ve used tribulus supplements as a means of increasing testosterone levels report that they often experience spontaneous erections. Whether that response arises from testosterone or from an effect of nitric oxide, the substance increased by the drug Viagra, isn’t clear. Testosterone and Growth Hormone:

Age Differences

Testosterone injections are known to increase growth hormone levels in young boys and older men, but the effects in younger men, over age 20, aren’t clear. A new study compares two doses of testosterone and its effects on growth hormone response in older (60 to 82) and younger (20 to 40) men.2 For three weeks the men were injected with either saline solution or doses (100 milligrams or 200 milligrams) of testosterone enanthate, a long-acting testosterone preparation.

The study found that giving the older men testosterone led to increases in all measures of growth hormone release, along with an elevation in insulinlike growth factor 1 (IGF-1) levels. The testosterone, however, had no effect on GH release in the younger men. IGF-1 did rise by 20 percent in the younger men and 40 percent in the older, but that was related to an increase in estrogen levels produced by aromatization, or enzymatic conversion, of the testosterone into estrogen.

The suggested mechanism for how testosterone increases GH levels in older men involves a blunting of somatostatin, a substance known to block growth hormone release. Why that didn’t occur in the younger men remains a mystery. That’s good news for older men, since they’re often relatively deficient in both growth hormone and testosterone, leading to detrimental changes in body composition and brain function. Testosterone Stimulation From Plants?

Various natural testosterone-stimulating substances derived from plants have been suggested over the years. Perhaps the most prominent is Tribulus terrestris, which is thought to promote testosterone secretion by stimulating the release of luteinizing hormone (LH) from the pituitary gland. LH controls the rate of testosterone synthesis in the testes. Many suggested plant ‘anabolics’ have not fared well when examined under the cold eye of objective science. But some plants may work as advertised.

Two plants found in western Africa, Hibiscus macranthus and Basella alba (the latter is also known as country spinach), are good examples. They’ve been used in several African countries for years as folk medicine for promoting male fertility, and this led scientists to measure their effectiveness.

Rats were given both leaf and water-based extracts of the plants.3 The water-based extract proved considerably more potent. In rats given both types of extracts, testosterone levels rose by 80 percent by the 15th day. Examination of the rats’ testes cells showed that the rate of testosterone synthesis rose by 136 percent. The plant extracts showed no evidence of toxicity, and no rats died as a result of taking the extract. The authors suggest that the plant extracts increased testosterone levels through a direct effect on the testes’ Leydig cells, the site of testosterone synthesis.

The obvious question is whether those plant extracts will produce similar testosterone-boosting effects in humans. Since they’ve been used for that purpose for many years in Africa, the next question is, When will they appear in supplement form?

References

1 Gauthaman, K., et al. (2002). Aphrodisiac properties of Tribulus terrestris extract (protodioscin) in normal and castrated rats. Life Science . In press.
2 Gentili, A., et al. (2002). Unequal impact of short-term testosterone repletion on the somatotropic axis of young and older men. J Clin Endocrinol Metab. 87:825-834.
3 Moundipa, F.P., et al. (1999). Effects of aqueous extracts of Hibiscus macranthus and Basella Alba in mature rat testis function. J Ethnopharmacology. 65:133-39. IM