Sunday, August 21, 2011

BODYBUILDING PHARMACOLOGY : Prostaglandin Perspectives by Jerry Brainum

Until biochemist and budding entrepreneur Barry Sears published his original diet book Enter the Zone, few people besides molecular biologists had ever heard of eicosanoids. Eicosanoids encompass several subtypes, all of which are synthesized in the body from dietary fatty acids. They include prostaglandins (so named because they were initially discovered in the prostate gland), thromboxanes and leukotrienes. They work a bit like hormones but are far more evanescent, being produced locally in a tissue and degrading within minutes.

Research shows they’re involved in just about every known body function, from blood pressure regulation to protein metabolism. They also interact with various hormones. For example, prostaglandins are involved in testosterone synthesis and release, as well as in the anabolic actions of growth hormone and insulin. Eicosanoids exist in a delicate balance in the body, and when certain ones are overproduced or underproduced, serious medical problems arise.

An example of this is the balance between prostacyclin and thromboxane A3 in blood-clotting function. Prostacyclin prevents excessive internal blood clotting, while thromboxane promotes clotting. Most heart attacks and strokes are initiated by a clot that is blocking, or occluding, an artery. An imbalance between thromboxane and prostacyclin causes clotting.

Among the eicosanoids synthesized in the body from dietary fatty acids is arachidonic acid, and many of the prostaglandins are made from it. The body can make it from omega-6 fatty acids, which are found in some vegetable oils, as well as such high-protein foods as meat and eggs.

In the body, arachidonic acid is stored in cellular membranes, but only the free, or unbound, version is subject to conversion into eicosanoids. The enzyme that releases arachidonic acid is phospholipase A2. Another enzyme system, cyclooxygenase (COX), converts the arachidonic acid into various eicosanoids. Insulin stimulates the activity of phospholipase A2, which helps explain why the Zone diet revolves around limiting insulin release through carbohydrate and fat control.

Why would you want to limit the production of eicosanoids? Some of them promote inflammation and pain in the body. Cortisol-based drugs control inflammation by inhibiting the activity of phospholipase A2 and promoting lipocortin. All nonsteroidal anti-inflammatory drugs, such as ibuprofen and even aspirin, work by blocking the activity of COX enzymes, which convert arachidonic acid into eicosanoids.

Eicosanoids are also involved in muscle growth and breakdown. One prostaglandin, called prostaglandin F2-Alpha (PGF2), is known to promote muscular growth. PGF2 is released during heavy exercise, particularly the type that causes the most pain and muscle-fiber damage—eccentric, or negative, reps with heavy weights. It’s also released during a pronounced stretch of a trained muscle, which is one reason that doing short, limited movements doesn’t do much for muscular size.

Information about the potent effects of PGF2 on muscle growth didn’t escape some intrepid bodybuilders. A veterinary form of injectable PGF2 is available under the trade name Lutalyse, which is intended to either induce ovulation or terminate pregnancies in cows. The fact that it’s never been approved for human use in the United States didn’t dissuade bodybuilders from using it. The prospect of muscular growth was too alluring.

Injecting PGF2 causes immediate smooth-muscle contractions, including the smooth muscles that surround arteries. Shortly after injecting the drug, the pain becomes evident, producing a pronounced burning sensation in the injected area. Some who’ve used the drug report feeling sore, as if they had the flu. Since PGF2 causes immediate broncoconstriction, or a tightening of smooth muscle in the lungs, those with any tendency to asthma or other breathing problems can find themselves in serious trouble quite rapidly.

Smooth muscle promotes movement in the gastrointestinal tract and the bladder. Injecting Lutalyse can cause a sudden and uncontrollable urge to defecate or urinate. Others experience cramping and diarrhea and just an overall feeling of illness. For women, using the drug will reliably produce the mother of all uterine cramps, since the uterus is basically a bag of smooth muscle. Recall that one of the drug’s medical purposes is to induce abortion—now you can understand why. When this stuff is injected, anything in the uterus will be expelled with the force of a pass by Joe Montana in his prime. And, guys, that also includes anything that’s in your intestines if you get greedy and inject too much at once.

Asthmatics and others with any type of breathing problem should not even consider trying this drug, no matter how strongly it promotes muscle growth. Same is true for women. For those who don’t mind feeling sick most of the time, the usual suggested starting dose is 0.5 milligram. The drug is injected into any muscle you want to grow, but avoid injecting it anywhere near the gut, unless you want to crap or pee in your pants within seconds, and I’m not kidding.

Since prostaglandins work locally, or in a paracrine fashion, and rapidly degrade, the effect of the injected drug doesn’t last long. The recommendation is to take it three to five times a day, gradually increasing the dose to one to five milligrams. You must rotate the injection sites; the injected area will hurt like hell. Don’t try to train the muscle you injected, as it, too, will be in extreme pain for a while.

Some bodybuilders combine a fast-acting insulin injection, such as Humulin-R, with Lutalyse, to promote a synergistic anabolic effect. Anecdotal reports say that PGF2 injections offset the fat-promoting effects of insulin, and published medical literature shows that this prostaglandin does inhibit bodyfat synthesis. One Internet article a few years ago said that PGF2 actually destroys fat cells, making you wonder why so many people are wasting time dieting or having expensive liposuction procedures.

Still another report says that PGF2 will “open up closed androgen receptors,” which suggests it’s an ideal antidote for those in whom too many anabolic steroids have closed androgen receptors. On the other hand, you’re advised not to consider taking PGF2 in conjunction with any type of steroid, since the resulting muscle congestion and pain will make it difficult to train any involved muscle.

I believe that Lutalyse is a drug for the highly motivated, in whom the quest for massive muscles isn’t limited by such little things as nausea, pain and just plain feeling like crap. Other drugs—anabolic steroids, growth hormone and even insulin—are a walk in the park compared to this stuff. Not to mention the possibility of an early return to wearing diapers—the adult kind. Then there are those who are just into pain and feel that the end justifies the means. The same mind-set that would readily administer a cellular poison and weed killer such as DNP (used for fat loss) in which the “therapeutic dose” is very close to the fatal dose would no doubt have no compunction about using PGF2; heck, bring on the sudden crapping and pain if it means bigger muscles. Full speed ahead.

The rest of you can get the benefits by training hard and heavy, using prestretch in your exercises, and ingesting the raw material from which PGF2 is made—omega-6 fats. I’d veer toward a source such as primrose or borage oil, since it provides the benefits of omega-6 fats with less inflammatory effects. Interestingly, omega-3 fatty acids, such as those found in fatty fish or as alpha linoleic acid in flaxseed oil, inhibit the formation of PGF2 because they divert the production of prostaglandins from arachidonic acid into another pathway. The net effect is less inflammation but no PGF2.

It may be a good idea not to ingest any omega-3 sources too close to a workout. Also, since various nonsteroidal anti-inflammatories, such as ibuprofen (Advil, Motrin and others), aspirin and newer COX-2 inhibitors like Celebrex, all prevent the synthesis of PGF2, they, too, should be avoided both before and after a workout. Wait a few hours before taking in omega-3 fats or these painkillers if you want to derive the significant benefits of naturally produced PGF2.

Natural Thyroid Stimulation and Inhibition

The thyroid gland, located in the middle of the neck, controls metabolism. The main thyroid hormones are triiodothyronine (T3) and thyroxine (T4). Of the two, T3 is considered five to seven times more biologically active than T4. Some scientists even consider T4 more of a pro-hormone for T3. Nearly all T4 is produced in the thyroid gland, while 85 percent of T3 production occurs in the liver and kidneys. In the liver the enzyme 5-iodothyronine deiodinase removes an iodine atom from T4 to convert it into the more metabolically active T3. The enzymes involved in that conversion require the presence of nutrients, especially selenium and zinc, as well as vitamin A. And of course, the raw material for thyroid hormone itself must be present: the amino acid L-tyrosine and the trace mineral iodine.

Competitive bodybuilders often take thyroid drugs, such as Cytomel (T3) or, less often, Synthroid (T4), prior to a contest in the belief that it will aid fat losses and thus produce a higher degree of muscular definition. The practice does have some scientific justification. Burning more calories than you consume, or taking in 40 or fewer grams of carbohydrates, leads to the production of reverse T3, a version of thyroid hormone with no metabolic activity. The body does this as a survival mechanism to prevent loss of lean tissue from too few calories or carbs. When that happens, your metabolism drops faster than your stock in Martha Stewart Living.

The main problem with using thyroid drugs is that you must take in more than your body normally produces to get a heightened metabolic effect. Taking doses equal to what’s normally produced in your body merely turns off normal thyroid output. Taking larger doses, however, produces a state of hyperthyroidism, which leads to a greater oxidation of all fuels, including protein. That means you can lose muscle. Most bodybuilders have found that out and have learned how to adjust thyroid dosages accordingly.

They also often use thyroid in conjunction with growth hormone. The growth hormone synergistically balances the thyroid effect, blunting catabolism while retaining the higher metabolic effect. In some cases, it’s even necessary to take thyroid (most often T3 drugs) because two weeks of GH injections blunt the release of thyroid-stimulating hormone (TSH), a pituitary gland peptide (protein) hormone that controls thyroid output. Thyroid hormone also works with testosterone and insulin in promoting an anabolic effect in muscle.

A few natural thyroid supplements are on the market. One is composed mainly of phosphate, since some studies show that phosphate may prevent the drop in metabolism that leads to dieting plateaus. Others include tyrosine, which makes up two-thirds of thyroid hormone, the other third being iodine, which functions solely to synthesize thyroid hormones.

Research shows that certain herbs, such as olive leaf and guggul, can also favorably affect thyroid function in a safe and effective manner. One study, using mice, shows that a combination of herbs, specifically ashwagandha, bauhinia and guggul, can increase T3 and T4 hormones by 108 percent and 55 percent, respectively, more than in a control group.1 That combination of herbs didn’t put stress on the liver function, but it did increase the antioxidant systems of the body, an effect linked to efficient thyroid hormone synthesis. The herbal extracts also enhanced the conversion of T4 into T3.

Another study found that various flavonoids found naturally in fruits and vegetables inhibit the enzyme that converts T4 into T3.2 The study design, however, featured an in vitro, or isolated-cell, design, and while the effect may possibly be duplicated in the body, it isn’t yet known how much flavonoid intake would inhibit thyroid function. Another study showed that flavonoids in green tea can do the same thing, but massive amounts of green tea are required for the effect.

Other foods containing natural thyroid inhibitors include peanuts and brassica veggies, such as broccoli and cabbage, though you’d have to eat relatively vast amounts of these foods to adversely affect thyroid function. In addition, these foods include nutrients—including flavonoids—that research shows offer potent protective effects against cancer and cardiovascular disease. Brassica veggies also contain substances that neutralize excess estrogen. So while you don’t want to overconsume such foods, it would be foolish to cut them from a healthful diet because you’re concerned about thyroid-inhibiting effects.


1 Panda, S., et al. (2000). Combined effects of ashwagandha, guggulu, and bauhinia extracts in the regulation of thyroid function and on lipid perioxidation in mice. Pharm Pharmacol Commun. 6:141-43.

2 Ferreira, A.C.F., et al. (2002). Inhibition of thyroid type-1 deiodinase activity by flavonoids. Food Chem Toxicol. 40(7):913-917.

©,2013 Jerry Brainum. Any reprinting in any type of media, including electronic and foreign is expressly prohibited. 

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