Bodybuilding News & Discussion > X3M HeadQuarters in English

Anabolic Research Update

<< < (2/5) > >>

Polomac:
IGF-1: Killer or Savior?

Insulinlike growth factor 1 is so named because of its resemblance to insulin. IGF-1 is synthesized both in the liver and in muscle. There are two variants of the hormone in muscle, and each is a potent stimulator of satellite cells, which are muscle stem cells and are required for muscle repair and growth. Most scientists say that IGF-1 is the primary anabolic effector of growth hormone, and GH stimulates IGF-1 synthesis in the liver. Scientists are looking at IGF-1 therapy with great interest, as it appears to reverse many of the effects of aging. As with GH, IGF-1 concentration drops with age, and many older people have 50 percent less than younger people do.

Numerous studies show that maintaining an optimal count of IGF-1 forestalls many of the typical signs of aging. For example, a lack of IGF-1 is linked to heart failure, which affects more than half of those over age 60. IGF-1 is also required to maintain brain cells, or neurons. Without a sufficient amount in the brain, neurons undergo a cellular suicidal process called apoptosis. Insufficient IGF-1 also makes muscles and connective tissue break down, resulting in the weakness and stiffness that older adults often experience.

With all these benefits, you’d think that just about every person over age 40 who’s low in the hormone would be supplementing it in some way. Thus far, however, commercial forms of IGF-1—which must be injected, as the hormone is protein based and composed of 79 amino acids in a particular sequence—are prescribed only to treat certain forms of childhood growth problems.

Because IGF-1 spurs cellular growth, some scientists voice concern that at high concentrations it could stimulate cancer. Indeed, higher amounts of IGF-1 are associated with certain forms of cancer, such as those of the prostate, breast and colon. The big debate among researchers is a chicken-and-egg argument: Does IGF-1 promote tumor growth and spread, or do tumors themselves increase IGF-1? IGF-1 is useful to tumors because it prevents their apoptosis.

Complicating the cancer connection is the fact that teenagers, still in a growth stage and thus producing large amounts of IGF-1, have low rates of cancer. By contrast, older adults have the highest rates of various cancers yet also have the lowest blood IGF-1 counts. A more rational scenario is that while IGF-1 doesn’t cause cancer, taking it in large doses may result in tumor activity. One recent study found that higher levels of IGF-1 are inversely associated with testicular cancer.1

Also confusing IGF-1 as a health issue is the way some animals react to the hormone. Studies with worms and other invertebrates show that a lack of IGF-1 helps extend life. Mice and rats deficient in IGF-1 live longer than rodents not deficient in it. Female mice having defects in IGF-1 cellular signaling appear to age more slowly than other rodents. Animal studies, however,  usually involve lifelong exposure, which isn’t the case with human studies. The hormone may also act differently in relatively short-lived animals, such as mice and rats, than in longer-lived humans.

Preliminary studies of IGF-1 with human subjects have shown beneficial effects. For example, researchers recently examined the effects of IGF-1 on human mortality.2 Critics of IGF-1 and GH therapy often say that rather than offering a fountain of youth, the hormones may hasten death, citing the longevity of some animals that are hormone deficient. In the eight-year human mortality investigation of IGF-1, which involved 376 healthy subjects aged 73 to 94, higher amounts of IGF-1 were associated with longer life and reduced cardiovascular risk. Those with the least IGF-1 in their bodies showed nearly twice the risk of death of those who had more. Those who had a lot of age-related overall body inflammation were particularly at risk; IGF-1 appears to douse the flames of out-of-control inflammation. Inflammation plays a major role in nearly all causes of premature death, including cardiovascular disease, cancer and such degenerative brain diseases as Alzheimer’s and Parkinson’s.

One major theory of why we age relates to cellular structures called mitochondria, the site of energy production and fat oxidation. Because mitochondria are the cell’s power supply, when they die or cease to function, so does the whole cell. The main cause of mitochondrial death is oxidation. The high rate of energy production in mitochondria also generates the highest rate of free-radical production in the body. By-products of oxygen metabolism, free radicals attack cell membranes. Mitochondria have extensive fat-based membranes, making them particularly prone to oxidation.

If you can maintain mitochondria as you age, the process of aging should slow down, as should the incidence of age-related degenerative disease. A new study shows that one way that IGF-1 may retard aging is by protecting mitochondria.3 Loss of mitochondria isn’t usually an issue in young people because of their higher IGF-1 counts. In the study, giving IGF-1 to aging rats normalized mitochondrial oxidative damage and function while reducing free-radical generation.

Another study done by the same researchers also provided low doses of IGF-1 to aging rats.4 Old rats deficient in IGF-1 have a lack of serum antioxidants, which were restored with IGF-1. Older rats also have more glucose, insulin, fat and cholesterol in their blood. All those metabolic abnormalities were corrected when the rodents got low doses of IGF-1. What happened in the study is important because insulin resistance increases with age and is often linked to a loss of lean mass, mainly muscle. Insulin resistance results in insulin spikes in the blood, which are linked to premature aging and diabetes, itself a cause of premature death.

The study also showed that old rats suffer brain and liver damage because of inadequate antioxidant defenses, but the low IGF-1 dose normalized antioxidant protection as well as mitochondrial dysfunction. Low-dose IGF-1 also increased testosterone, not a minor effect for anyone who wants to maintain muscle size and strength with the passing years.

Does that mean you should consider taking IGF-1 injections as a means of slowing the aging process?  If you’re deficient in the hormone, you will more likely be given GH itself. Since GH increases IGF-1, the benefits will be similar. Also, most physicians have more experience in providing GH than IGF-1, so the optimal doses of GH are better established. Drug forms of IGF-1 were approved by the United States Food and Drug Administration in 2005, but one form was removed from the market in 2007, leaving only one (Increlex) available. Athletes and bodybuilders have used a form called long R3 IGF-1 for years. It’s structured to last longer in the blood, thus extending its active time.

Taking too much IGF-1, as some bodybuilders and athletes do, could lead to problems. The primary side effect of large doses of IGF-1 is hypoglycemia, or low blood sugar, which points up similarities between insulin and IGF-1. In other words, large doses of IGF-1 could start to act like insulin. That isn’t likely to happen with IGF-1 drug forms that also include IGF-binding proteins, which extend and delay the activity of the hormone. Unlike insulin, IGF-1 doesn’t stimulate bodyfat synthesis, although it does stimulate internal organ growth, resulting in the bloated abdomens you see on some athletes. That occurs only with doses far bigger than you’d ever use for antiaging purposes. The same holds true for GH: Small doses are beneficial, but large doses place you in unknown biophysical territory.

In the near future gene therapy will be available for placing IGF-1-producing genes directly in muscle. Preliminary studies with rodents show startling gains in muscle size and a 35 percent increase in strength with the technique. The idea is that the therapy will eliminate the extensive weakness and loss of muscle that come with age, turning 70-year-old muscle back into 19-year-old muscle. Even so, the technique is experimental with humans and needs refining. Attempting to try it now could lead to catastrophe, such as turning on cancer-friendly genes.

For now, take solace in the fact that regular exercise is the most potent method of maintaining an optimal measure of IGF-1; weight training is the best form of exercise for that. A high-protein diet is also directly related to IGF-1, with lower protein intake linked to less total IGF-1 in the body. Some studies suggest that taking DHEA, an adrenal steroid, can normalize low IGF-1 and may be the reason that DHEA is often called an antiaging hormone.

How to Live to 90 or More

A study published last February in the Archives of Internal Medicine included some tips on how to live to 90 or more.5 Twin studies found that one-fourth of the variation in human life span is attributed to genetic factors, which means that 75 percent of life span is linked to modifiable risk factors. The research involved 2,357 men who participated in an ongoing project called the Physicians’ Health Study. At the beginning of the study in 1981, the men, average age 72, provided such information as height, weight, how often they exercised, blood pressure, cholesterol counts and so on. Twice during the first year and then once a year through 2006, they completed a questionnaire about changes in their habits, health status and ability to complete daily tasks.

A total of 870 men, or 41 percent, lived to age 90 or older. Those who made it to that age had a negative relation to several preventive risk factors—most related to common sense—such as not smoking, not having diabetes, not being fat and not having high blood pressure. Their positive relation to exercise, meanwhile, was particularly effective. The authors suggest that a 70-year-old man who doesn’t smoke, has normal weight and blood pressure and no diabetes and works out two to four times a week has a 54 percent probability of living to age 90. With the presence of adverse factors in his profile, his probability of living to 90 was reduced by the following amounts:

• Sedentary lifestyle, 44 percent

• Hypertension, 36 percent

• Obesity, 26 percent

• Smoking, 22 percent

• Three factors—such as no exercise, being fat and having diabetes—14 percent

• Five other factors, 4 percent

The primary point of the study is that if you adhere to a healthful lifestyle as you age, your chances of living longer are enhanced. Conversely, having favorable genetics but living an unhealthful lifestyle can shorten your life. One example of that was the former king of late night TV, Johnny Carson, who came from a family of long-lived adults, with both his father and grandfather living past 90. Carson, however, was a heavy smoker most of his life and also drank too much alcohol. Such behavior took its toll, overruling Carson’s favorable genetics. He died at age 79 from the effects of emphysema related to his cigarette smoking.

References

1 Chia, V.M., et al. (2008). Insulin-like growth factor-1, insulin-like growth factor-binding protein 3, and testicular germ-cell tumor risk. Am J Epidemol. 167:1438-1445.

2 Brugts, M.P., et al. (2008). Low circulating IGF-1 bioactivity in elderly men is associated with increased mortality. J Clin Endocrin Metab. 93(7):2515-2522.

3 Puche, J.E., et al. (2008). Low doses of insulin-like growth factor-1 induce mitochondrial protection in aging rats. Endocrinol. 149(5):2620-2627.

4 Garcia-Fernandez, M.G., et al. (2008). Low doses of insulin-like growth factor-1 improve insulin resistance, lipid metabolism, and oxidative damage in aging rats. Endocrinol. 149(5):2433-2442.

5 Yates, L.B. (2008). Exceptional longevity in men: Modifiable factors associated with survival and function to age 90 years. Arch Intern Med. 168:284-290.  IM
http://www.ironmanmagazine.com/site/?p=706

Polomac:
IGF-1: Is It the Real Deal?
February 3, 2010 by Jerry Brainum

Insulinlike growth factor-1 is so named because of its resemblance to insulin. It consists of 70 bonded amino acids, which makes it a protein-peptide hormone. That means that like growth hormone, IGF-1 must be injected. Otherwise it degrades in the gut, rendering it useless.

IGF-1 is considered the key to growth hormone’s anabolic effects, and GH release promotes its synthesis in the liver. The liver also synthesizes six binding proteins that work with IGF-1, with one, IGFBP-3, being the primary IGF-1-bonding protein in the blood. A substance called the acid-labile subunit prevents the premature degradation of IGF-1. The complex of IGF-1, binding protein and the acid-labile subunit extend the time that IGF-1 lasts in the blood to 15 hours or more—compared to the 10 minutes that unbound IGF-1 lasts.

Because IGF-1 is so similar to insulin, it can interact with insulin cell receptors and produce some of the same effects as insulin. In fact, the primary side effect of both excess insulin and IGF-1 is hypoglycemia, or low blood glucose, although insulin is 10 times more potent than IGF-1 in that effect. When you train for an extended time—more than one hour—the liver upgrades its release of IGF-binding protein 3 to prevent the onset of hypoglycemia that would otherwise ensue because of the increased release of IGF-1. IGF-1 also amplifies the action of insulin, even at low doses. Insulin helps maintain blood IGF-1 by boosting the synthesis of IGFBP-3.

The primary role of IGF-1, though, isn’t to transport glucose into cells, as in the case of insulin. Instead, it fosters cellular division and growth. It’s also involved in cell repair, particularly in brain, heart and muscle. Its function in cell division has led many scientists to suggest that IGF-1 has a role in several types of cancer. That makes sense, since cancer is a process of uncontrolled cellular division; however, the evidence for that is not yet definitive by any means. True enough, IGF-1 inhibits apoptosis, or cellular suicide. Out of that you get the theory that tumors would upgrade synthesis of local IGF-1 to keep themselves alive and thereby encourage the spread of cancer throughout the body. Yet some researchers suggest that it’s a classic chicken-and-egg scenario, in that IGF-1 doesn’t cause cancer but is instead produced by tumors.

Meanwhile, studies show that people low on IGF-1 have a greater chance of dying from a heart attack. That’s because IGF-1 prevents the death of heart cells and offers protection when the cells are highly stressed, as occurs during a heart attack.

While the liver synthesizes IGF-1 and packages it with the binding proteins for transport into the blood, two variants of IGF-1 that are produced in muscle, one of which is called mechano growth factor, play a major role in muscle gains. They spur the activity of other proteins that are involved in muscle protein synthesis and encourage the activity of muscle stem cells, called satellite cells, which repair damaged muscle—and training does damage muscle. In fact, intense weight training is a primary stimulus of the release of IGF-1 in muscle. (Another protein, myostatin, prevents muscle growth by interfering with satellite-cell proliferation.)

A recent study used specially bred mice that produced only tiny amounts of IGF-1 in their livers, 75 to 85 percent lower than normal mice.1 Despite that, they show normal growth patterns and development. Their bodies compensate by secreting a lot of GH.

The IGF-1-deficient mice have low bodyfat and tend to stay lean as they age. The reason they make so much GH is that IGF-1 is the primary feedback inhibitor of GH release from the pituitary gland. Less IGF-1 in the blood equals more GH release from the brain. Interestingly, human studies show that testosterone also blunts the IGF-1 signal to the brain, thus helping maximize the effects of GH. That’s likely one reason why GH is considered synergistic with testosterone and anabolic steroids, which are synthetic forms of testosterone.

But back to the mice. The lack of systemic release of IGF-1 doesn’t affect its local production in muscle. Researchers showed that by having the mice engage in resistance exercise. No, the mice didn’t do any barbell curls or squats. They climbed a ladder with tiny weights attached to their bodies—a 16-week rodent weight-training routine. Another group of mice not deficient in IGF-1 did the same exercise. The groups produced equivalent muscle gains. The researchers concluded that systemic IGF-1 produced in the liver isn’t required for muscle hypertrophy. The IGF-1 forms produced in muscle following exercise are the important ones.

Bodybuilders and other athletes have been using IGF-1 injections for years. The drug is often used along with GH, anabolic steroids and insulin. One popular formulation is Long R3IGF-1, which is thought to be more potent than IGF-1 produced in the body. The hormones can interact with cellular receptors only when they’re free, or unbound from their plasma-binding proteins. Because the Long R3 IGF-1 lasts longer in the blood than natural IGF-1, it could present a serious threat to health. The free IGF-1 can interact with tumors, causing cancer progression. It could also convert a benign or inactive tumor into an active one. Another experimental form of IGF-1 said to be used by athletes is des(1-3) IGF-1. It’s a short form of IGF-1 that is not protein-bound and is often directly injected into muscles, and it’s rumored to lead to hyperplasia, or the splitting of muscle fibers to form new fibers. It’s strictly conjecture, as there is thus far zero proof of the effect in healthy athletes.

The prescription form of IGF-1 is mecasermin, trade name Increlex. Manufactured using recombinant DNA technology, it’s used to treat IGF-1 deficiency and growth problems. Increlex is also prescribed for patients who have developed antibody resistance to GH therapy. Unlike Long R3 IGF-1, Increlex is identical to natural IGF-1, retaining the 70 amino acid sequence of IGF-1 that the body produces.

Although it appears that only the version of IGF-1 produced in muscle has any true anabolic effects, many bodybuilders and athletes who’ve used IGF-1 claim to have benefited from the drug. There is no scientific evidence for that, but there is some evidence of benefits for people deficient in IGF-1.
Hormone-deficient patients who get IGF-1 experience increased rates of fat loss and fat oxidation. What causes that isn’t known, but one theory is that the IGF-1 may suppress circulating insulin. In addition, fat cells contain IGF-1 receptors, so the hormone can interact with fat cells.

From the standpoint of protein synthesis, IGF-1 injections provide the anticatabolic effects of insulin combined with the increased protein synthesis induced by GH. Like insulin, IGF-1 encourages amino acid uptake into muscle cells. It stimulates peripheral tissue uptake of glucose, which lowers blood glucose levels. It also suppresses liver glucose production, which is actually good for those who are insulin resistant, since the liver under that circumstance tends to produce too much glucose, which perpetuates the insulin insensitivity and can eventually result in diabetes. Indeed, IGF-1 is being considered as a diabetes-prevention drug.

From an athletic point of view, IGF-1 may share insulin’s role in increasing glycogen synthesis, which powers intense training. Possible side effects of IGF-1 injections include jaw pain, facial and hand swelling and heart-rhythm disturbances. The last-named effect is more likely if doses of more than 100 micrograms are injected. That can cause the heart to stop beating (yikes!) and blood pressure to drop dramatically. The effect is caused by an IGF-1-induced drop in blood phosphate and can be prevented by administering phosphate with the IGF-1. An increase in IGF-1 caused by either GH or IGF-1 injections is thought to play a major role in producing the repulsive bloated abdomen seen on some competitive bodybuilders. Adding insulin to the stack exponentially increases the chance of that particular side effect showing up. Note that all internal organs have an extensive supply of both insulin and IGF-1 cell receptors. Providing an abundance of either or both hormones will lead to organ growth, contributing to the abdominal bloat.

Several factors affect IGF-1 production in the body. Insufficient protein or calories cause it to plummet, and excess calories may cause it to increase. One study of normal-weight women who overate found a 19 percent increase in IGF-1 after two weeks of gorging, with 46 percent of the bodyweight gain attributed to lean mass and 54 percent to bodyfat. Fasting insulin doubled in the women, and testosterone levels rose significantly. Thus the lean mass gain produced by overeating could be the result of an increase in IGF-1, insulin or testosterone—or all three. I would quickly add that overeating is not a good method of adding muscle mass, as most of the weight gain consisted of bodyfat. It does, however, explain why bulking up was a popular technique for gaining mass among bodybuilders of the past and, to a certain extent, those of today. Other nutrients necessary to maintain IGF-1 in the body include the minerals magnesium and zinc and thiamine, a.k.a. vitamin B1. Zinc is particularly important.
Exercise boosts IGF-1. Some studies suggest that the antiaging effects of DHEA use come from an increase in IGF-1 in the body. IGF-1 maintains both muscle and connective tissue, as well as brain and heart cells, so it’s not a stretch to think that having more IGF-1 will make you feel and possibly look younger. Recent human studies confirm the antiaging effects of IGF-1 and GH. Yet animals deficient in IGF-1 live longer and show no cancer whatsoever. Clearly, that’s an example of how animal physiology may differ from that of humans. On the other hand, countless people who’ve used GH therapy say that they feel younger, but that’s rarely evident in their appearance. Excess bodyfat is associated with lower IGF-1 and GH. One recent study examined lifestyle factors that affect IGF-1 in college-age women and found a positive correlation with soy protein and the mineral selenium.2 Drinking alcohol blunted the effects of IGF-1 in the women.

The greatest future use of IGF-1 will without doubt involve gene therapy, which directly places genes that produce IGF-1 in muscle, usually by attaching them to an inactive virus or vector that penetrates the muscle cells. Studies with young mice show that the procedure results in a 15 percent increase in muscle mass, along with a 14 percent increase in strength. Gene therapy in old mice led to a 27 percent increase in strength, along with a total regeneration of aged muscle. In another mouse study, the IGF-1 gene was placed in the animals’ glutes and calves, which resulted in a 17 to 115 percent increase in muscle-cross-sectional area. One hopes the growth occurred mainly in the calves rather than the glutes!
Studies with the muscle-specific form of IGF-1 have yielded similar or better results. Some scientists speculate that once the procedure is perfected for humans, it will spell the end of age-related muscle weakness and frailty. They foresee an 80-year-old man who can produce the same muscle gains as a 19-year-old. Older people don’t gain as much muscle as younger people because satellite cell activity either doesn’t occur or is ineffective. That defect is completely repaired with IGF-1 gene therapy.

Some predict that gene therapy will replace drugs as the main form of doping in the future. No one has any idea of how to detect gene therapy doping yet. The only possible way would be a muscle biopsy, but even that would prove problematic because complete uptake of the IGF-1 gene may not occur, and the biopsy may reveal just normal muscle tissue.

Rumors abound that some athletes have already subjected themselves to IGF-1 gene therapy. That isn’t hard to believe when you consider that one of the therapy’s developers, H. Lee Sweeney, Ph.D., of the University of Pennsylvania School of Medicine, says he’s besieged by athletes and coaches from around the world who offer to be his guinea pigs. In truth, however, the technique is not ready for prime time, for some earlier gene-therapy experiments resulted in patient deaths. Future subjects could experience fatal immune reactions to the vectors used to place the gene in the body. Another danger is an inability to control the expression of the gene, which could translate into a rapidly spreading cancer. Or the expression of the gene could extend from skeletal muscle into heart muscle, resulting in excessive heart muscle growth that portends premature heart failure.

Last and perhaps not least, while IGF-1 injections work great on paper, real-world results are mixed. Most athletes suggest that using IGF-1 alone does little or nothing to boost muscle gains, which makes sense in light of the mouse study that linked only local muscle IGF-1 to mass gains. Many steroid manuals suggest that IGF-1 injections are best used with other anabolic agents, such as GH, testosterone and insulin. In that case, how do you ascertain just how well IGF-1 is working? The gains attributed to IGF-1 may in fact result from the other drugs in the combo. Nor can you discount the placebo effect. If you think something will work and truly believe that it will, it often does. Perhaps those who tout the “massive muscle gains” they’ve allegedly made from IGF-1 injections made those gains because they trained harder and believed from their head down to their diamond-shaped calves that the drug would work.

And for them, it did. Or did it?

References

1 Matheny, W., et al. (2009). Serum IGF-1-deficiency does not prevent compensatory skeletal muscle hypertrophy in resistance exercise. Exp Biol Med. 234:164-170.
2 Karl, J.P., et al. (2009). Diet, body composition, and physical fitness influences on IGF-1 bioactivity in women. Growth Hor IGF-1 Res. In press.

http://www.ironmanmagazine.com/site/?p=4780

Polomac:
Anabolic Research Update: The New Anti-Estrogens
One of the areas of medicine in particular that has seen a lot of progress is the field of breast cancer treatment. Researchers here focus heavily on the reduction of estrogenic activity in the body, as estrogen inhibition can help the disease by starving breast cancer cells that are responsive to this hormone. Their work has spawned several new commercial drug products that are very effective in this regard. Since anti-estrogenic drugs are also widely used by bodybuilders for side-effect mitigation and as hardening/cutting aids, I thought it would be of interest to take a look at a few of the new drugs that have hit the market in recent years. In think you’ll find that the agents discussed here not only hold a great deal of promise, but may even bring us to places that the old-standard anti-estrogens simply could not.

 

Fareston (toremifene citrate)

Fareston is an estrogen receptor antagonist with mixed agonist/antagonist properties. It’s classified as a “SERM,” which is short for Selective Estrogen-Receptor Modulator. It is specifically a nonsteroidal triphenylethylene derivative, similar in structure and action to both Nolvadex (tamoxifen citrate) and Clomid (clomiphene citrate). Fareston is used for the treatment of breast cancer in postmenopausal women with estrogen-receptor positive or estrogen-receptor unknown (unsure if the cancer is estrogen responsive) tumors. It works by attaching to the estrogen receptor in various tissues, blocking endogenous estrogen from exerting biological activity. This agent in the newest mixed estrogen receptor agonist/antagonist to get our attention in the bodybuilding world, and was approved by the FDA in 1997.

Like Nolvadex, Fareston has an added benefit of being somewhat intrinsically estrogenic in the liver. This allows it to support positive changes in serum cholesterol values, an effect tied to estrogenic activity. It may turn out, however, that Fareston is the measurably better agent of the two in this regard. One study, for example, compared the lipid altering effects of tamoxifen and toremifene in a group of 49 postmenopausal women. Standard oral doses of either tamoxifen (20 milligrams) or toremifene (60 milligrams) were given to the patients for a period of three years.

Both antiestrogens caused a significant reduction in serum total and LDL (bad) cholesterol levels, however the change in HDL/LDL ratio (the more important measure) was much more favorable with the Fareston group. This drug caused an increase in HDL cholesterol levels by 14 percent, whereas tamoxifen use in this case actually decreased HDL values by five percent. In the end, the toremifene group noted much more favorable changes in serum lipid profiles and cardiovascular disease risk. It may turn out to be that Fareston is the antiestrogen of choice for the heart-conscious athlete.

 

Faslodex (fulvestrant)

Faslodex is one of the newest weapons in the war on estrogen, approved by the FDA in 2002 for the treatment of estrogen receptor positive breast cancer. It’s a highly selective estrogen receptor antagonist (it’s also classified as an estrogen receptor downregulator). This means it does not target the production of estrogen, but like Nolvadex and Clomid, prevents this hormone from being able to exert activity in the body by blocking available receptors. Faslodex seems well equipped to compete with even some of the newer aromatase inhibitors. One study, for example, shows Faslodex to be as effective in Arimidex in treating breast cancer patients who have already failed with first line endocrine treatments.[ii] Another shows the drug to prevent tumor cell turnover and growth significantly more effectively than tamoxifen citrate.[iii] Studies investigating the physiological response to Faslodex made note that its strong actions allow it to downregulate estrogen receptor concentrations, and progesterone receptor concentrations as well.[iv] Clearly, when it comes to anti-estrogens, Faslodex is far more advanced than the “standard-issue” agents we have been using in the bodybuilding world for years.

There are only two real drawbacks to Faslodex. For one, it’s a pure estrogen receptor antagonist, not a mixed agonist/antagonist. This makes is quite different from Nolvadex or Clomid, drugs that actually tend to improve serum cholesterol values because they act as estrogens in certain tissues like the liver. Although I have been unable to find studies looking at cholesterol levels in response to Faslodex, knowing how closely tied estrogen is to the synthesis of HDL cholesterol, I can only assume it will have as strong an influence (negative) here as do aromatase inhibitors.

The other major problem is price. A single five milliliter injection runs over $900 at the pharmacy. I guess when you make a medicine that people are only going to need once per month, you aren’t going to make millions on it if you sell it for $50. Mind you, I have no knowledge of how costly this drug is to manufacture, but if I had to guess I would think the price has much more to do with how much the company thinks they should get from a patient on a monthly basis. Since it’s expensive, of course, there is little chance this drug will catch on with the bodybuilding public.

 

Aromasin (exemestane)

Aromasin is a steroidal suicide aromatase inhibitor, extremely similar in structure and action to formestane. It works to lower estrogen production in the body by blocking the aromatase enzyme, which is responsible for synthesizing estrogens. The FDA approved Aromasin in late 1999 for the treatment of advanced breast cancer, specifically in post-menopausal women whose disease has progressed following therapy with a first line agent such as tamoxifen. It’s given only to post-menopausal women because before menopause most of a woman’s estrogen comes directly from the ovaries, not aromatization (aromatase is the principle source of estrogen after menopause). Aromasin is being advertised as the only “aromatase inactivator” available, which ignores the fact that formestane is sold as an over-the-counter nutritional supplement in the U.S. right now. Although both these agents essentially do the same thing in the body, Aromasin does the job far more effectively.

Aromasin may be the most effective aromatase inhibitor available to date, in fact. While Arimidex boasts of estrogen suppression around 78 percent in its packaging insert, Aromasin reports it can lower estrogen as much as 85 percent on average.[v] Feedback from bodybuilders tends to support the preference for Aromasin over other aromatase inhibitors, so this may very well be the case. Regardless of which one is the true “king,” all of the newer aromatase inhibitors— Arimidex, Femara, Aromasin— should be looked at as extremely effective for reducing estrogen synthesis in the body. A possible 10 percent difference in inhibition between the weakest and the strongest of the three is really not going to amount to all that much during your next cycle. If you are looking at one of these agents to prevent gynecomastia and help you lose fat and water on your next cycle, they are all going to do a good job for you. If you absolutely need the best agent, my money would be on this one.

 

 

 

 

Antiatherogenic effects of adjuvant antiestrogens: a randomized trial comparing the effects of tamoxifen and toremifene on plasma lipid levels in postmenopausal women with node-positive breast cancer. Saarto T, Blomqvist C, Ehnholm C, Taskinen MR, Elomaa I. J Clin Oncol 1996 Feb;14(2):429-33

 

[ii] Fulvestrant, Formerly ICI 182,780, Is as Effective as Anastrozole in Postmenopausal Women With Advanced Breast Cancer Progressing After Prior Endocrine Treatment. Howell A, Robertson JFR, Quaresma Albano J, Aschermannova A, et al. J Clin Oncol. 2002; 1:57.

 

[iii] Fulvestrant, an estrogen receptor downregulator, reduces cell turnover index more effectively than tamoxifen. Anticancer Res. 2002 Jul-Aug;22(4):2317-9.

 

[iv] Fulvestrant. Cheung KL, Robertson JF. Expert Opin Investig Drugs 2002 Feb;11(2):303-308

[v] High activity and tolerability demonstrated for exemestane in postmenopausal women with metastatic breast cancer who had previously failed on tamoxifen treatment. Kvinnsland S, Anker G et al. Eur J Cancer 2000 May;36(8):976-82

 
Black Market Update

Weratestone 250. This particular product contains testosterone enanthate, in a concentration of 250mg/ml. Weratestone is made by the French pharmaceuticals manufacturer Weimer Pharma, however it is not available for sale on the domestic prescription drug market in France. Instead, it is exported to French-speaking countries in Africa, such as Algeria, Zimbabwe and Mozambique. This steroid very rarely circulates in the United States, however it’s found from time to time in Western Europe. Testosterone enanthate is, of course, one of the most abundantly manufactured steroids worldwide. It’s also one of the most frequently counterfeited, and indeed many of the more popular brands in Europe, such as Testoviron, Primoteston and Testosteron Depot, are copied with alarming frequency. Although glass ampules such as the one Weratestone 250 comes in are by no means difficult to duplicate, the less than popular nature of this particular brand has kept it pretty low on the counterfeiters’ radar. So long as your source is otherwise reliable, you can probably trust this item when located.

Shown also this month is a counterfeit vial of nandrolone decanoate that’s supposed to originate in Russia. It is listed to contain the steroid in a concentration of 200mg/ml, and holds a nicely sized 10ml volume of oil. Farmadon, who is labeled to have made the drug, was a real company operating in the steroid business at one time. It has been closed for a couple of years, however, and definitely did not make this product. When it did make anabolic steroids, it packaged them in very odd, tall and thin glass ampules, not 10ml multi-dosed (American-style) vials like this. It appears that an underground manufacturer, who is believed to be in Russia, has simply taken up the abandoned name and started producing a number of different products including this Deca, nandrolone phenylpropionate, testosterone enanthate, testosterone propionate, and a Sustanon clone. The contents of these products have not yet been verified, but judging by the positive feedback, they probably do contain some amount of real steroid. –WL

 

 http://www.musculardevelopment.com/articles/chemical-enhancement/2061--anabolic-research-update-the-new-anti-estrogens.html

Polomac:
 Important  “Medical Mistakes” to Avoid During Your Next Cycle!

 

Anabolic Doc

By Thomas O’Connor, M.D.                 

 

Important “Medical Mistakes” to Avoid During Your Next Cycle!

Part 1

                                               

            Hey folks, it’s the Anabolic Doc coming at you for another information-filled article. Even though I have been with Muscular Development for only a few months, all I can say is that it has been super exciting. I would first like to thank Steve Blechman for giving me the opportunity to lead the “Anabolic Community” with true medical direction and guidance. For years our “Brothers and Sisters in Iron” have had to deal with a lot of their medical problems on their own. Getting valid information from a doctor even willing to monitor your anabolic steroid and performance-enhancing drug regimen and do their best to keep you healthy, has been nonexistent. This is where I come in, because I am willing to put it all on the line to make sure that you get the best medical care in the world when you are one of my patients.

            I always get e-mails asking what kind of things should be avoided during a cycle from a medical perspective. We have all read these boring articles on basic ideas of what to do and not do during a cycle to help improve your results. But this series is going to take it over the top and won’t be like anything you have ever read before. I am going to discuss with you the most important medical mistakes to avoid during your next cycle. I am going to touch on some very basic ideas first off, because many of our readers here at MD may be planning their very first cycle.

            You may be familiar with some ideas that I present in this series, and many of them will not be so familiar. A lot of powerlifters and bodybuilders avoid these issues out of ignorance, or sheer laziness. Next, I will discuss some advanced information as well, to help those who may be doing more intricate stacks that even a top pro bodybuilder could relate to. I am going to cover the most important mistakes that I see in my clinical practice that athletes who do use performance-enhancing drugs are guilty of committing. I am going to give you the real deal here, people. I am not just going to sprout off some textbook info at you, hoping you can decipher heads or tails of what I am about to explain.

            Remember, I want to be scientific in my explanations, but I know that the majority of the readership at MD is not doctors or scientists but hardcore bodybuilders who want to know as much about the “Anabolic Science” and its medical application and health prevention. With this, you can expect me to help you understand the science of medicine in relation to anabolic steroid use and their side effects. I will be presenting things in layman’s terms as well, so everyone can truly take advantage of all the information that I have to offer.

 

Time to Be Responsible

            Now before I get to discussing the medical mistakes that I want cover with this issue, it is imperative to know that as a strength athlete who has decided to go to the dark side and incorporate performance-enhancing drugs into their program, I want you to be responsible. Now when I say responsible, I don’t mean to be responsible to pay your cable bill on time or to make sure you take out the garbage. I am also not talking about being responsible about making sure you fork over half your paycheck every week for child support, due to that one-night-stand you had with that exotic dancer named Bambi, while you were blitzed into a Jager Bomb coma. I just hate those fucking DNA tests; oops sorry— I fell off track there for a minute.

            No, I am talking about being responsible for taking care of your health. When I say health here I am not talking about today or tomorrow, I am talking about thinking about the next 20-plus years of your life. Oh, I know the scene and what happens in the shadows of anabolic enhancement, so you should know that I am not one of those uptight asshole doctors who wears his smock around his office with his nose turned up at you. No, I am nothing of that sort. In fact, I detest that arrogant type of attitude and when you deal with me, you are guaranteed a warm smile and a true sincere doctor who wants the best for your competitive career and your long-term health.

            The problem with many strength athletes, both bodybuilders and powerlifters, is the fact that they do not think about the long-term consequences of their actions. They only think of what is happening right now— today. Like I mentioned earlier, this is the wrong attitude to have because remember, you reap what you sow. The decisions you take today may come and bite you on the ass like a rabid pit bull tomorrow, so you have to make sure that you always think of the possible repercussions of choices.

            Now, I don’t want to sound like one of those guys who harps on things, but the reality is, as a patient of mine or even one who reads my columns, I want you to take responsibility for your health. With this said, let’s now take a look at what the ‘Anabolic Doc’ has to offer!

 

Not Getting Blood Work Done

            This right here is the most important piece of information that I am going to give you, bar none. This is the first and most critical thing you are going to do to keep yourself healthy. No, I am not saying this so you come and see me so I can bill you— not at all. This is not my intention in the least. No matter who your doctor is, you must get this done at least twice per year as a minimum. This includes a full panel of things like your cholesterol, both HDL and LDL. Your blood pressure, triglycerides, homocysteine levels, liver values, and kidney function should also be monitored regularly, among others.

            This is the bare minimum that you should do to know how your organs are functioning. How do you know what is going on with your body and your organ health if you don’t get checked at least a couple times per year? Now I know some bodybuilders who are more responsible do this, but I still know that it is not more than 20 percent of those who use steroids. The biggest offenders in this arena are powerlifters. I know you are my “Brothers in Iron,” but the fact remains that way too many of you are lazy asses and don’t get this done at all. Hell, I have had world-class powerlifters come into my office and they have been using steroids close to 14 years and not once have they ever got their blood work done. What the hell is that!? This, in my opinion, is the most irresponsible thing you could do. Now not only is this irresponsible for you— but what about your wife and kids? Don’t you owe it to them to at least try and take care of your health?

            Like I mentioned earlier, if you decide to tread down the “Anabolic Path,” then you have to be responsible for your actions. You can’t do something like go on 30 cycles over a decade of use and abuse and then think, “Hey maybe I should get some blood work done to see if my liver isn’t bloated like a fucking dead horse.” I hate to say this, but if this is you or your current mental state, then you are going to pay the fucking piper and pay him with your ass if you don’t step up to the plate and be a true man about taking care of your health.

            Now you may be thinking that the Anabolic Doc is some type of arrogant prude, but no, I am not. I truly care for your health and want you to be the best competitive athlete you can be— but at the same time, I want you to realize that you are taking prescription-strength drugs to enhance your performance. That 50 mg of Thai Dbol that you chugged down this morning with your oatmeal were not “Hot Tamales” (I just loved that candy as a kid), so you cannot take this lightly. These are serious medications, (some more than others, and you will see this when we start discussing insulin and thyroid drugs) so you cannot just think that you can just do whatever you want and get away with it for years on end. This is not the case.

            You may think you are a bad-ass because you weigh 260 pounds with 8 percent body fat, but listen to me closely here for a minute. When one of your organs fails, or another major health ailment takes you down, then you will see right away that you are not made of molten steel, but flesh and bones. Even the biggest bad-ass can be brought to his knees when even a simple medical ailment hinders his body from functioning the way it should. So please, no matter if you can bench press 600 pounds or if your arms are 23 inches, don’t let this make you think that you are indestructible. Because when reality hits you in the face like a bitch slap from a pimp on 125th and Highland Avenue, you will wish you listened to the Anabolic Doc and the important message he tried to convey!

 

Using Underground Steroids

            Now I can see all of the cyber experts reading this now and saying, “This guy doesn’t know the reality of the scene, man— he’s out of his environment.” No actually, I am not out of the scene, you 21-year-old ass-clown, because I have been in the underground trenches longer than you have been alive. I knew the ins and outs of anabolic pharmacology and the underground street scene when your mother was wiping your ass. So don’t give me any of your ignorant rhetoric. Now you may be thinking how he can say that in a time like this, being the fact that most readers live in the United States. OK, let me explain.

            I fully understand what is going on in the scene at the underground hardcore level. I know what happened with Operation Gear Grinder back in 2005; they put a major halt on much of the veterinary-grade gear coming out of Mexico that supplied 90 percent of the black market in this country. Quality Vet, Denkall, Animal Power, Brovel, Tornel, SYD Group and others were the major players in the U.S. steroid black market. This major bust ultimately caused the massive increase of clandestine labs to be set up and hence the underground craze that started in this country.

            But first you have to look at the medical perspective. Do you really know where your stuff is being made? No you don’t! You could have some guy making this stuff in his garage with an environment that resembles a slum in Calcutta. This is what you want to inject into your body? No wonder so many guys are getting abscesses like it is going out of style. Cleanliness is of utmost importance— not only so you don’t get an abscess that erupts like Mount Vesuvius but also for you organ health. If you think you are doing your kidneys any favors by injecting dirty gear, think again, my friend.

            Didn’t you ever wonder what years of injecting dirty shit could do to your organs? Sterile prep conditions are only one of the problems you could run into. What about metals, carcinogens and contaminants? We all know that the majority of raw powders that these underground labs use come from China. Now, if you have watched the news over the last couple years, you know that they don’t have the best reputation for quality control.

            OK, let me see— the lead paint used in children’s toys or the melamine in the baby milk formulas? Close to 300,000 Chinese babies were affected and became ill over this whole melamine scam that took place in the baby formula scandal. Six of these babies died with still several hundred in critical condition because of major kidney shutdown. If they are willing to cut corners to save money and risk a major health crisis like this in their own country, what is their compassion toward bodybuilders living in the U.S.?

            MMM… if they don’t give a rat’s ass about all these contaminants that even go out to their own people, including babies, then are they going to care if they send Bob Smith living in “Butt-Fuck Idaho” some Test Enanthate powder laced with mercury, lead or PCBs? The answer is a big FUCK NO! Think about this for one minute here and take note, as this is a serious matter. PCBs, which are known as polychlorinated biphenyls, consist of close to 210 different chemicals that have similar structures. They were developed in 1929 and used for many different industrial purposes. The problem with this stuff is that it is super-resilient; it takes forever to break down. 

            Now this is where it gets juicy. The International Agency for Research on Cancer has stated several times that being exposed to PCBs can increase your chances for cancer and listen up here folks, specifically liver and kidney cancer! If this doesn’t make you sit up and take notice, I don’t know what will. From tests done that I have seen, many of the underground labs do contain an abundance of heavy metals and other contaminants and this was confirmed by our own Team MD writer William Llewelyn.           Think about that for a minute, my friends. Not only do you not know the conditions in which your underground gear is made, you also don’t even know the company the powder is coming from in China or the conditions in which it is manufactured. Maybe the same company that is pumping hormone powders on the black market is making a chemical that is carcinogenic in the same manufacturing equipment. How do you know? Then you are getting trace remnants of that carcinogen in your gear powder and then you guys back home in the heart of America are injecting this into your bloodstream. Scary, isn’t it!? I bet you didn’t think of that scenario the last time you bought a bottle of underground Deca from your boy “Big Mike” in the change room of your local gym.

            Now I know you are going to break my balls and tell me that it’s hard to get real pharmaceutical gear and all that. I know the reality of the scene and the product that was available in the ’80s and ’90s that was American-made and all the goodies from Europe are no longer a viable option. So I understand that those who use steroids in America are between a rock and a hard place. But in the end, that doesn’t change the fact that you could be introducing potent carcinogens into your system via injection because Mao Lee in Shanghai doesn’t give a “flying Commie fuck” if your raw hormone powder contains impurities that will give you cancer in 10 years. Nothing replaces real pharmaceutical gear for performance and health, and that is the bottom line!

 

Take My Words to Heart

Now with this installment, I covered some basic but very important mistakes that are critical for maintaining your health during your next cycle. Even though they are very elementary in nature, how many of you reading this who do use anabolic steroids avoid them? I know many of you and I am not talking about just the beginners, but also the veterans in the sport have fallen prey to these anabolic blunders. I hope that I have opened up some eyes with this issue and have actually made you think about what you are doing in your path to build that ultimate physique. Like I said from the beginning, if you take this path in life, you have to be fully aware of the consequences and you must do all that you can to prevent health conditions down the road.

 

Anabolic Doc 411

            Now one of the additions to my regular column is the Anabolic Doc 411. This will be a nice little segment about me and my personal practice. Here you can take a glimpse inside what I am currently up to with my clients and personal life. Here I will give you some insight on what is going on with my training program to break yet another record in the bench press. You can look forward to my opinions on some different topics and what is currently going on in the media with the “War on Steroids” propaganda that is launched day in and day out in this country. So starting next month, get ready for some interesting hardcore snippets into the life and times of the Anabolic Doc!

 

References:

            www.usdoj.gov,DEA Leads Largest Steroid Bust in History.

            Buckley C, More than 54,000 Affected by Milk Scandal, National Post.

            Polychlorinated biphenyls (PCBs) [CAS Number 1336-36-3]. Integrated Risk Information System (IRIS), 1997.

            Llewellyn W, Counterfeit Analysis Report, Muscular Development.
http://www.musculardevelopment.com/articles/chemical-enhancement/2192-important-medical-mistakes-to-avoid-during-your-next-cycle.html

Polomac:
 Anabolic  Pharmacology: Equipoise - Anabolic Androgenic Steroid

 

Anabolic Pharmacology

By Seth Roberts

Equipoise

 

Pharmacology is the study of drugs and their effects. Anabolic pharmacology is the study of drugs that have a growth-promoting effect in muscle. This column will explore anabolic pharmacology by profiling a different anabolic drug and its effects each month. The focus of discussion this month will be the anabolic androgenic steroid, Equipoise.

Boldenone is a 1-dehydro derivative of testosterone that has been sold as a veterinary preparation under the name Equipoise, and is largely known by this name. The formation of a double-bond in the 1,2 position changes the shape of the molecule slightly. This also changes the potency and characteristics of the molecule. Boldenone has a lower affinity than testosterone for the androgen receptor, making it less potent on a milligram-for-milligram basis.1 This steroid can be converted to estrogen, but less so than testosterone. In addition, boldenone is metabolized to 1,4 dienedione, which is a potent aromatase inhibitor.

Boldenone is converted by 5-alpha reductase to 1-testosterone, a more potent steroid, as well as to the 5-beta isomer— which is thought to be an inactive metabolite.2,3 Binding to sex hormone-binding globulin (SHBG) is much lower with boldenone than with testosterone, meaning a larger free plasma concentration but a shorter half-life in plasma.4 There is little-to-no binding to progesterone or glucocorticoid receptors, and no real data on the interaction of boldenone with the different enzyme systems.1

The undecyclenate ester of boldenone was the ester marketed under the original trade name. In recent years, the free base and other esters have become available as underground preparations. On the street, Equipoise is erroneously considered to have the same activity as Deca and is often substituted for Deca in a stack. Dan Duchaine, if not the originator of this myth, at the very least propagated it in his book Underground Steroid Handbook II. If you look at the structure, you can see that boldenone is structurally identical to dianabol without the C-17 alkylation.

Most people experience much less side effects with boldenone, compared to methandrostenolone. This is because boldenone converts to estradiol, while methandrostenolone converts to methylestradiol. Methylestradiol is a much more potent and long-lasting estrogen than plain estradiol. Since there is no C-17 alkylation, there is no liver toxicity associated with boldenone. Boldenone is rumored to be very good at increasing red blood cell production. While all androgens stimulate erythropoiesis, there is no evidence in the scientific literature that boldenone is superior in producing this effect.5,6,7,8

Boldenone undecyclenate is generally injected every four or five days, but some people will inject every day while others will inject once per week. The longer half-life of the undecyclenate ester would dictate an injection frequency of every 10-14 days, but there has been a trend toward more frequent dosing by anabolic-androgenic steroid (AAS) users, even with drugs known to have long half-lives. Dosing is generally kept pretty low (300-500 milligrams per week), but the low binding affinity would argue for twice that dosage, taken with testosterone.

The anabolic-to-androgenic ratios are favorable for boldenone, but people do not consider boldenone a particularly potent steroid— possibly due to the low doses that are utilized. Also, boldenone does not cause much water retention— so many people assume it is not working if they do not put on 10 pounds in one week. Boldenone is said to cause an increase in vascularity, although there is no mechanism to explain why boldenone would do this more than any other AAS.

Seth Roberts is a former pharmaceutical research scientist with over 10 years of pharmacological research in the discovery and development of novel therapeutics. If you want to learn more about Anabolic Steroids, pick up Seth’s new book Anabolic Pharmacology at www.Ergogens.com. [© Seth Roberts, 2009. All rights reserved. For informational purposes only, not to be considered as medical advice or an endorsement of the use of illegal substances.]

 

References:

1. Ojasoo T, Delettre J, Mornon JP, Turpin-VanDycke C, Raynaud JP: Towards the mapping of the progesterone and androgen receptors. J Steroid Biochem, 27(1-3):255-69, 1987.

2. Schanzer W, Donike M: Metabolism of boldenone in man: gas chromatographic/mass spectrometric identification of urinary excreted metabolites and determination of excretion rates. Biol Mass Spectrom, Jan;21(1):3-16, 1992.

3. Schanzer W: Metabolism of anabolic androgenic steroids. Clin Chem, Jul;42(7):1001-20, 1996.

4. Saartok T, Dahlberg E, Gustafsson JA: Relative binding affinity of anabolic-androgenic steroids: comparison of the binding to the androgen receptors in skeletal muscle and in prostate, as well as to sex hormone-binding globulin. Endocrinology, Jun;114(6):2100-6, 1984.

5. Gorshein D, Murphy S, Gardner FH. Comparative study on the erythropoietic effects of androgens and their mode of action. J Appl Physiol, 35(3):276-8, 1973.

6. Paulo LG, Fink GD, Roh BL, Fisher JW. Effects of several androgens and steroid metabolites on erythropoietin production in the isolated perfused dog kidney. Blood, 43(1):39-47, 1974.

7. Sanchez-Medal L, Gomez-Leal A, Duarte L, Guadalupe Rico M. Anabolic androgenic steroids in the treatment of acquired aplastic anemia. Blood, 34(3):283-300, 1969.

8. Alexanian R. Erythropoietin and erythropoiesis in anemic man following androgens. Blood, 33(4):564-72, 1969.

http://www.musculardevelopment.com/articles/chemical-enhancement/2175-anabolic-pharmacology-equipoise.html

Navigacija

[0] Indeks poruka

[#] Sledeća strana

[*] Prethodna strana