DNP: Still Dangerous After All These Years By Jerry Brainum

En route to a call that came in from a local gym, paramedic Mack Jackson ponders what the emergency could be. As an amateur bodybuilder himself, Mack knows what can happen in a gym. A weight falling on someone’s foot. A newbie exerciser overexerting him- or herself on the treadmill. Perhaps it’s someone who unknowingly became dehydrated on this warm summer day by not drinking enough water during the workout.
    Arriving at the gym, Mack and the other paramedics are directed to a muscular 22-year-old bodybuilder, who’s prostrate in a corner of the gym floor. As the medical crew begins to examine him, someone says, “He was training intensely, but then he stood up and hit the ground like someone hit him on his head.”
The patient is clearly lethargic, weak and has vomited a few times. When questioned, he seems confused but does manage to reply to questions about prior medical history, use of medications, allergies and other things that might explain his present condition. Nothing seems obvious; however, some clues emerge from his appearance. His skin is flushed and hot, and he is sweating profusely. While sweating is hardly unusual in a warm gym, it’s the color of his sweat that catches the medics’ collective attention: It’s a pale yellow that’s also apparent on his white T-shirt. Initial examination reveals a rapid heart rate and elevated blood glucose level.
    Another member of the gym gathers the bodybuilder’s belongings and checks his locker. As the paramedics move the bodybuilder into the waiting ambulance, the gym member hands Mack the patient’s clothes, along with a bottle of capsules filled with a yellow powder and a page printed off the Internet titled “DNP for Fat Loss.”
     On the way to the hospital the bodybuilder’s temperature rises to 104 degrees. Noting that, the paramedics increase body-cooling measures, such as removing his clothes and putting ice packs on his groin and under his arms. The air-conditioning in the ambulance is also set to maximum. The EMT crew radios the hospital that they may have a toxicological emergency coming in. They are told by a hospital physician to keep the patient still and calm and continue giving him intravenous fluids.
     Even with the supportive measures the bodybuilder’s temperature continues to rise. At the hospital he develops pulmonary edema—fluid in the lungs—suffers damage to his liver and heart, along with kidney failure,then slips into cardiac arrest and dies.
     The healthy young bodybuilder had succumbed to the effects of 2,4 dinitrophenol, or DNP, a popular and extremely dangerous substance touted for producing dramatic and rapid fat loss. Rumors abound that DNP is the secret weapon that many pro bodybuilders use to get ripped in a relatively short time. In fact, a few years ago an elite pro bodybuilder contacted me about using it in preparation for the Mr. Olympia contest.
I advised against it, informing him of the dangers, but he’d found out that another top pro was a regular user of DNP and insisted on trying it himself. He referred me to a man who later became notorious for distributing designer steroids to world-class athletes. That man was going to supply and encapsulate the DNP for him. Within a few days, however, the bodybuilder called me back and told me that he had abandoned the notion of using DNP in his preparation for the Olympia because it made him feel very ill and weak. He was one of the lucky ones; he survived.
     DNP first attracted attention in 1919 after French munitions workers began experiencing unexplained massive fat losses. They were exposed to DNP while making explosives consisting of 40 percent DNP and 60 percent TNT. DNP is chemically similar to TNT and is a precursor of the latter compound. The workers also showed other symptoms, such as malaise, headaches, dizziness and night sweats.
     During the 1930s doctors who were aware of the effects of DNP on the French munitions workers wondered whether it could prove useful as a weight-loss drug under controlled conditions. Sure enough, initial studies showed that a daily dose of 300 to 400 milligrams of DNP for only two weeks resulted in metabolism increases that ranged from 36 to 95 percent over baseline levels. That contrasted with thyroid hormones, which increased metabolism an average of only 10 percent above normal.
     The initial studies reporting on the fat-loss potential of DNP were all short-term, with none lasting more than three months. Those early researchers noted that they couldn’t predict toxic effects with extended use. Sure enough, other studies began appearing that showed that DNP was hardly innocuous. A 1933 issue of the Journal of the American Medical Association told of a severe skin reaction in a woman who took DNP for two weeks. A 50-year-old Viennese doctor in San Francisco took an overdose of it for weight-loss purposes and cooked himself from the inside. After using a prior, lower dose of DNP without incident, he had opted for a dose that was beyond the suggested safe range. When told by another physician that he should avoid being so reckless again, the Viennese doctor said that he would take a higher dose, and if it killed him, he would just be “another martyr to science.” While he didn’t exactly become a medical martyr, he did die an agonizing death.
    In the early 1930s DNP was a popular weight-loss drug, with an estimated 100,000 people using it over a period of 15 months. More than 1,200,000 capsules were dispensed from one clinic in San Francisco, and more than 20 companies sold it under such trade names as Nox-Ben-ol, Nitroment, Nitraphen, Redusols, Formula 17, Slim, Dinitrenal ,and Dinitrole. Those proprietary formulas were sold in drugstores without a prescription, warnings or usage directions. Only New Jersey, Louisiana and California required prescriptions to obtain DNP.
    While initial problems related to this substance were at first thought to be related to careless use, more serious toxic reactions began appearing, including skin rashes, a severe depression of white blood cell count, jaundice and disturbances in the senses of smell and taste. Several people, such as the previously mentioned doctor, died after using DNP. That led to a 1934 warning issued by the Food and Drug Administration. Although the FDA could do little more than warn about possible toxic effects, its experts were also analyzing various products, finding that DNP was often an unlisted ingredient.
    In 1935 an epidemic of cataracts occurred, mostly in young women who had used DNP for fat loss. Some cases occurred months or years after the last dose. One ophthalmologist estimated that more than 164 people were affected in that manner. Newspapers featured such headlines as, “Blinded by Weight-Loss Drug,” and “Anti-fat Drug May Cause Blindness.” In 1938, with the passage of the Federal Food, Drug and Cosmetic Act, the FDA was granted enforcing powers and promptly removed DNP from the market. Prior to passage of that law, the FDA had prepared a special exhibit for Senate committee hearings. Called the chamber of horrors, the exhibit included several deadly substances sold on the market, including DNP.
While DNP lost its legal status as a weight-loss drug by the FDA action, it remained in use in industrial settings, as a wood preservative, in photo developing, and as a weed killer. In the 1970s Russian workers manufacturing a pesticide that included it as an ingredient became ill. A 1982 medical journal reported that DNP as an ingredient in herbicides led to “undiagnosed fevers.”
     Around the same time, DNP reemerged in the bodybuilding world under the name Hexalon. The distribution was limited to professional bodybuilders, who were warned not to exceed the suggested dosage or death could ensue. That dire warning didn’t dissuade any of the athletes who used it, since they were also told that when used properly, Hexalon would burn off fat at an unprecedented rate, making them appear cut to the bone. Those who used Hexalon often reported feeling as if they had the flu, with weakness and fatigue.
In Texas a Russian-born doctor named Nicholas Bachynsky was dispensing DNP, which he called Mitcal, at his chain of medical clinics. He claimed to have first learned about DNP in 1963 while translating Russian medical journals for the United States government. The Russians had given their soldiers DNP to help keep them warm in winter. The main side effect noted was weight loss.
     Bachynsky’s ads touted an average weight-loss of 15 pounds a week. The only side effect, the ads noted, was increased body heat. The ads also said no deaths had occurred with the use of Mitcal, though one weightlifter had committed suicide by overdosing on it in 1984. According to Bachynsky, DNP “decreased useful energy production, thus making an overefficient metabolism very inefficient.” The treatments cost an average of $1,300 each—though DNP is a relatively inexpensive chemical.
Although Bachynsky asserted that no one had died from his treatment, he hedged his bets by having prospective clients sign a waver that warned of blood clots,, cataract formation, hemorrhage, allergic reactions and, yes, even death. Clearly the small print was ignored by those who envisioned a 15-pound-a-week weight loss, since more than 15,000 people signed up for the treatment.
   In 1982 the FDA began receiving complaints from many of Bachynsky’s customers about such adverse reactions as fever, shortness of breath, dizziness and extreme sweating. FDA investigators who arrived at Bachynsky’s clinics in Houston noted that the pharmacy next door to the clinic—also owned by Bachynsky—stored bulk containers of dinitrophenol from Eastman Kodak Company that were labeled “For chemical purposes only, not for drug use.”
    In 1985 the Texas attorney general sued Bachynsky and his clinics, charging that the doctor had failed to advise his patients that Mitcal was not recognized as safe for weight loss, was highly toxic and not approved by the FDA. On March 21, 1986, Bachynsky was found guilty of drug violations and ordered to pay $86,000 in fines and fees. He was also issued an injunction against further use of DNP. In July he was charged with violating the injunction after it was learned that he was still dispensing DNP at his Dallas clinic. In 1990 Bachynsky’s medical license was revoked, and he was sentenced to 10 years in prison for insurance fraud.
    While you would think that after a few years in prison Bachynsky would steer clear of DNP, apparently that wasn’t the case. In 2004 he and three other men were charged by the Securities and Exchange Commission with eliciting fraudulent securities related to a company they were involved in called Helvetia Pharmacueticals. The Florida-based company purported to treat cancer using a “patented therapy involving heat to destroy cancer cells.” The treatment was called “intracellular hyperthermia therapy.” The key ingredient was none other than DNP.
    While in prison in the 1990s, Bachynsky became acquainted with Dan Duchaine, notorious as the "steroid guru." Dan was also serving a prison term and listened intently to Bachynsky’s accounts of his experience with DNP. The fat-loss attributes particularly intrigued Duchaine, and when he was released from prison, he publicly announced that DNP was the king of fat-loss drugs. Another era of DNP had begun, one that hasn’t abated since.
    DNP interferes with a process called oxidative phosphorylation that results in the production of the immediate energy substance of the body, ATP. DNP uncouples oxidative phosphorylation in the mitochondria, or energy-producing portion, of cells, and that leads to a frantic use of other available energy sources by the body, particularly bodyfat. The process doesn’t produce any useful energy, however, creating heat, or futile energy, cycles. The heat can quickly exceed the body’s capacity, thus explaining the inherent danger of DNP use. In addition, the body shifts to anaerobic glycolysis as the primary cellular energy source, producing enough acid by-products to lead to lactic acidosis.
    DNP can be absorbed through the skin, explaining how the original French munitions workers got it into their bodies, as well as the farmers who used it to kill weeds. The suggested use for fat loss often involves taking it one week on and one week off. The daily dose range is two to 10 milligrams per kilogram (2.2 pounds) of bodyweight. The lethal dose is estimated to be between one and three grams when taken orally, but the three-gram-dose effect is cumulative over a five-day period; that is, three grams taken over five days could easily prove fatal. For example, if a 100-kilogram person takes 600 milligrams, he can get to three grams by the fifth day. Many have followed the suggested “safe dosage guidelines” and found otherwise.
    In a case widely reported on the Internet, a 22-year-old man died after using the suggested dose of DNP (600 milligrams a day). He had taken the dose for four days prior to his death. The signs and symptoms of DNP poisoning look similar to those of heat stroke and heat exhaustion. Various supportive measures are used in a hospital setting, such as body cooling, providing drugs to prevent seizures and calm the patient, and providing a drug called dantrolene, which prevents the release of calcium in muscle. That prevents muscle contraction, which lowers body heat. Keeping the body cool is a key to preventing death by DNP. Although headache may be present in a person who took DNP, aspirin is contraindicated in this case, since aspirin is also a weak uncoupler of oxidative phosphorylation and would only worsen the patient’s condition or kill him or her.
    Shortly before his death from congenital kidney disease, Dan Duchaine touted a “natural” form of DNP called usnic acid that was derived from a lichen. A few companies sold usnic acid as part of a commercial fat-loss supplement; however, the stuff was hardly safe or harmless. Several cases of liver failure deaths resulted from people having used a supplement containing the "safe" usnic acid. Small wonder, since one study showed that usnic acid was 50 times more potent than DNP in interfering with ATP production. The FDA subsequently removed usnic acid from the market. At least one company defied the FDA removal order, and kept usnic acid in their fat-loss formula. A female fitness competitor used the supplement and developed liver failure, which led to her suing the company that sold the product.
   Scientists regularly use DNP as an effective cell killer, and some recent studies show that it can block the formation of beta-amyloid, a protein that causes Alzheimer’s disease. One recent study even showed new neuron growth from DNP. But those are all highly controlled studies done in a lab setting. For all other uses, such as inducing fat loss, DNP is truly a roll of the dice: If you win, you lose a lot of fat fast. If you lose, you lose your life. Even Las Vegas offers better odds than that.

                                                     References

¹ Leftwich, R.B., et al. (1982). Dinitrophenol poisoning: a diagnosis to consider in undiagnosed fever. Southern Med J. 75;182-184.
² McFee, R.B., et al. (2004). Dying to be thin: a dinitrophenol-related fatality. Vet Human Toxicol. 46:251-54.

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

 

 

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Two From Humana By Jerry Brainum

You’d think obtaining accurate information about sports nutrition would be simple, given the plethora of Internet sites that regularly discuss the topic. Unfortunately, I’ve found that most of the “information” online is based on anecdotal evidence or how any particular supplement is viewed by an individual—or thinly disguised commercial hyperbole. Many Internet forums are populated by company shills who claim unbelievable gains made after using certain supplements.

A major source of information for me over the years has been textbooks related to nutrition. Most are scientifically based and are not commercial in any way. Problem is, those texts are often poorly written or assume that readers have an academic background in biochemistry and chemistry.

More recent texts seem to have overcome these problems. Two perfect examples are Nutritional Supplements in Sports and Exercise and Essentials of Sports Nutrition Supplements, both recently published by Humana Press. They contain completely accurate and easily understood information and do not require you to have completed a college science curriculum.

Essentials of Sports Nutrition Supplements is the official textbook of the International Society of Sports Nutrition and is a study resource for obtaining a credential with the organization. Some of the chapters related to physiology tend to veer into technical language, but the meat and potatoes of the book—discussions of protein, fat, carbs and various supplements—are based on the latest published research, devoid of commercial overtones and easy to understand.

Nutritional Supplements in Sports and Exercise begins by discussing legal and psychological aspects of sports supplements, followed by chapters on the nutrient and hydration needs of athletes and those engaged in regular exercise. Part three holds special interest if you’re engaged in bodybuilding. You’ll find chapters on how muscle-mass and weight-gain supplements work, which weight-loss supplements are effective and which don’t work as advertised and effective nutrient combinations that help build muscle and strength without side effects. Other chapters discuss recovery supplements and meal timing. All the chapters are written in an easily understood style that requires no science background or technical expertise.

The books are particularly useful for personal trainers, coaches and anyone who wants to know the scientific details related to sports nutrition but doesn’t want to be assaulted by the commercial nonsense rampant in most other places.

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

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Creatine: Does It Prime or Pinch the Pump? By Jerry Brainum

    One indirect gauge of the effectiveness of sports supplements is the amount of criticism directed at them. Supplements that work as advertised seem to attract more attention. Examples include ephedrine-and-caffeine combinations that were banned for one year by the FDA due to often dubious adverse-effect reports, then restored to the market by a federal judge because of a lack of sufficient scientific evidence concerning their potential dangers to health when used in suggested doses, only to be banned again soon afterward. Another example is the pro-hormone supplements, which fell victim to the ongoing hysteria about anabolic steroids. The final versions of them were remarkably effective and produced few or no side effects when used as directed. Their biggest problem was that they attracted too much attention—and because a few of them actually were anabolic steroids or contained so-called designer steroids. That last generation of prohormones, officially banned in 2005, did prove to be toxic in many cases, especially to the liver. Small wonder they many turned out to be old, discarded steroids that were developed by drug companies, but never released.

     It was perhaps only a matter of time before creatine was accused of endangering health. That’s evident in reports that it is linked to kidney failure, muscle cramps and liver damage, none of which are even remotely true.

    Some reports to the FDA have even claimed that using creatine led to heart problems. Since creatine is a natural constituent of the human body, synthesized from amino acids in the liver, pancreas and kidneys, it’s hard to justify an accusation like that. Nevertheless, a recent case report linked the use of supplemental creatine to atrial fibrillation, a disturbance of heart rhythm.¹

    Atrial fibrillation involves a disturbance in the contraction of the atrial, or upper chambers of the heart. The incidence of this disorder doubles with each decade of life, so it’s far more common in older people. The most frequent cause is long-term hypertension, or high blood pressure, which may damage the heart. The errant heart rhythm may lead to more clots being released into the blood—embolisms that may then travel to the brain, inducing stroke. Doctors prevent that effect by providing anticoagulants, such as Warfarin, to those afflicted with the condition.

    When atrial fibrillation occurs without any evidence of structural heart damage, it’s called lone atrial fibrillation. While it’s rare in younger people, it can be produced by scar tissue forming in the atrial chambers of the heart, hypersensitivity due to neural stimulation of the heart or an inflammation in the heart. The most common causes, however, are drug use, including excessive caffeine intake, acute alcohol intoxication and using too much thyroid drugs (many bodybuilders have experienced it after using excessive amounts of the thyroid drug Cytomel).

     In the case study, a 30-year-old man without any prior evidence of heart problems reported to a hospital emergency room, complaining of heart palpitations and rapid breathing, both of which had occurred abruptly within the previous 48 hours. An electrocardiogram indicated atrial fibrillation. The man denied using any drugs, and none showed up in his medical tests. He did, however, admit to using creatine supplements. He’d begun by taking 20 grams a day for five days, a loading phase, followed by a maintenance dose of 2.5 grams daily for one month.

    That much creatine produced cramping and diarrhea, so he curtailed it for a month, then switched to a capsule form. He developed the heart symptoms while taking a loading dose of the creatine capsules. He was treated with intravenous drugs to prevent clot formation and to stabilize his irregular heart rhythm. That proved effective, as his heart returned to normal rhythm in eight hours. He was discharged within 24 hours and told to take aspirin and a beta-blocking drug for his heart.

     In discussing this man’s case, the author asserts that since creatine is known to cause dehydration and diarrhea, that may have caused an electrolyte, or mineral, imbalance that led to the atrial fibrillation. Yet the man’s primary electrolytes, potassium and magnesium, were within normal values. While it has been frequently reported anecdotally that creatine causes dehydration, there’s no documented evidence in the medical literature that points to it. Since creatine may promote a shift of water from extracellular to intracellular compartments in the body, it may adversely affect electrolyte balance that way, but that would happen only during restricted fluid intake. The odds that creatine would cause an effect significant enough to produce a lone atrial fibrillation are remote at best.

      So why did the man in the study experience atrial fibrillation after he took creatine? He may have had an inherent sensitivity to creatine, or the creatine may have induced a neural stimulation of his heart. The latter effect is more likely, since the man was a vegetarian, and vegetarians have lower creatine stores in their bodies. The loading dose may have had a druglike effect on him. The solution would be to avoid the creatine load, which is a dubious technique anyway, and take no more than five grams, or one teaspoon, a day. In 30 days that will result in the same level of creatine storage in muscle as a one-week load, minus any possible side effects.

    One other aspect to consider is that if anything, creatine would be beneficial for the heart. A feature of heart failure is the lack of production of energy compounds, such as ATP. Anything that boosts ATP production in the heart would aid heart function. Several supplements, such as coenzyme Q10, ribose and creatine, have all been shown to do just that.

¹ Kammer, R.T. (2005). Lone atrial fibrillation associated with creatine monohydrate supplementation. Pharmacotherapy. 25:762-764.

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

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Testosterone and Rapid Weight Loss by JERRY BRAINUM

In 1997 three collegiate wrestlers made national headlines by dying. The story was considered newsworthy not only because the three young men had no history of illness but also because of accusations that their use of creatine supplements had led to their untimely deaths. Subsequent investigation revealed that creatine had nothing to do with it. There was no evidence that they’d taken supplements in the days before they died. What really killed them was dehydration, leading to kidney shutdown in two of the wrestlers.

Making weight is common in many sports, and bodybuilders often try to reduce bodyfat before a competition in order to highlight muscularity. The sensible method of losing weight is a longer, slower process. Most professional bodybuilders begin their contest preparations anywhere from three to six months out from a contest; losing weight slowly preserves muscle and strength. Still, it’s not uncommon for athletes to resort to sudden-death techniques of dropping weight that, sadly, can result in just that. Few athletes pay the ultimate price for injudicious dieting and training, but they do pay in more subtle ways.

The cost of dropping weight too rapidly was highlighted in a recent study of 18 elite wrestlers who competed nationally and internationally.¹ Rapid-weight-loss programs are common in wrestling. Scientists monitored changes in the wrestlers’ body composition, body chemistry, minerals and hormones over the course of a two-to-three-week weight-reduction regimen.

The wrestlers—average age 21 with an age range of 17 to 31—were told to restrict their intake of carbohydrates and fat but keep their protein intake high, at two kilograms per pound of bodyweight, to prevent loss of lean mass. Their daily calorie intake was 800 to 2,000, and they stimulated dehydration during the last two days through heavy training and hot saunas, as well as restricting fluid intake and lowering their daily calories to a maximum of 1,000. The wrestlers also took various minerals:

• 500 milligrams of potassium five times daily

• 247.5 milligrams of magnesium five times daily

• 300 milligrams of calcium twice daily

Although the authors didn’t discuss it, the wrestlers were taking low-quality minerals. They used potassium chloride, which can have caustic effects in the gastrointestinal tract; magnesium hydroxide, which rapidly brings on diarrhea; and calcium carbonate, which is chalk and harder to absorb than other forms of supplemental calcium. Even so, getting some minerals is better than getting none. Odds are that their restricted diet was low on those minerals and that side effects would have been much more in evidence without them. Remember, the wrestlers were actively seeking dehydration to foster weight loss, and dehydration causes mineral loss.

The weight-reduction program proved successful. The greatest overall weight loss was 11 percent, along with an average 6.9 percent drop in bodyfat—not bad for only two weeks. The wrestler also lost 2.9 percent lean mass, which could be a combination of water and muscle.

Most alarming was the program’s effect on testosterone. The average drop was 33 percent, along with a 47 percent drop in luteinizing hormone, or LH, a pituitary hormone that controls testosterone synthesis. Even worse, the wrestlers’ sex hormone-binding globulin went up by 21 percent. SHBG binds active testosterone in the blood, and the more SHBG your body has, the less testosterone you have in your blood.

The fact that LH dropped by 47 percent reflects insufficient food intake, coupled with high stress conditions. Note that the wrestlers didn’t do any aerobics during their weight-loss program, only anaerobic exercise, such as weight training and wrestling practice. Increased aerobic exercise, especially when accompanied by an ultralow-calorie diet, is associated with low testosterone and higher cortisol counts. The wrestlers reported increased fatigue, tension and anger and reduced vigor. They also had trouble sleeping, and stress from that further depleted their testosterone.

Insulinlike growth-factor 1 did not take a hit. IGF-1 is vital for muscle repair. The authors think that the tapering exercise program the wrestlers used may have maintained their IGF-1, or perhaps the program didn’t last long enough to reflect any changes in that hormone. I would suggest two other possible mechanisms. IGF-1 is related to both calorie and protein intake. The wrestlers’ higher protein intake may have preserved their IGF-1, along with their continued training. In addition, the carbohydrate and fat may have spurred an increased release of growth hormone, which would be reflected by a higher amount of IGF-1.

The information in this study applies to bodybuilders who don’t use anabolic drugs. Natural bodybuilders who drop weight too fast by extreme dieting and training will likely experience rapid drops in testosterone and growth hormone, as well as a rise in cortisol. Result: significant muscle loss, along with a slowdown in bodyfat loss due to lack of anabolic hormone support and a drop in active thyroid hormone. So if you avoid pharmaceutical hormones, you should also avoid crash dieting, unless you also want to crash your muscle gains.

A World Without Estrogen

Bodybuilders hear a lot of bad things about estrogen these days. Its evil reputation is almost on par with cortisol, although the two hormones have little in common other than both being steroids. Steroids, in case you’re confused, refers to the molecular structure of the hormones and the fact that they’re produced from cholesterol. Estrogen, testosterone, cortisol, aldosterone and activated vitamin D are all steroids.

Judging by the number of supplements that claim to lower estrogen, it appears to be a definite liability for bodybuilders. In males having an abundance of estrogen is linked to water retention—caused by increased aldosterone and the resulting sodium retention—subcutaneous bodyfat and gynecomastia. The higher-than-usual estrogen seen in some bodybuilders is caused when aromatase, a ubiquitous enzyme found throughout the body but particularly concentrated in fat tissue, converts anabolic steroids to estrogen.

Bodybuilders who use large doses of anabolic steroids may have more estrogen than young women do. Normally, men have about 10 times as much testosterone as women, only 0.8 percent of which is converted into estrogen. That scenario changes in the presence of huge doses of anabolic steroids, which is why bodybuilders who juice also take drugs that either block estrogen cell receptors (Nolvadex), or inhibit the aromatase enzyme directly (Arimidex).

What’s frequently overlooked is that estrogen may have benefits. It appears to interact with androgen cell receptors, amplifying the impact of anabolic steroids. Estrogen also maintains IGF-1, which has anabolic functions in muscle besides helping muscle repair after exercise. Some emerging evidence shows that estrogen may play a role in preventing excessive muscle damage during exercise.

From a cardiovascular protection viewpoint, estrogen is a paradox. In women it appears to protect against cardiovascular disease by fostering higher levels of high-density lipoprotein, the good kind of cholesterol, and maintaining the elasticity of arteries. Having supple arteries helps protect against atherosclerosis and high blood pressure.

Purveyors of anti-estrogen supplements frequently advise getting off them because “estrogen offers cardiovascular protection in men,” but that idea doesn’t jibe with the latest research. In a recent study that involved 933 young men, average age 19, researchers looked at the connection between the sex hormones estradiol, estrone, testosterone and androstenedione and such major cardiovascular-disease risk factors as high blood cholesterol, high blood pressure and excess weight.² Positive links emerged between higher estradiol and total cholesterol, along with lower HDL. Having more estrone, a weaker estrogen, was linked with increased total cholesterol and heightened LDL, which is also linked to cardiovascular disease. Testosterone, which is often accused of promoting cardiovascular disease in men, had no effect on any risk factors.

When estrogens are given to older men in hopes of preventing cardiovascular disease, they usually increase they incidence of it. Clearly, estrogens are of no benefit whatsoever to men of any age. Why they appear to protect women from cardiovascular disease is still a biological mystery.

Some scientists suggest that increased estrogen, coupled with lower testosterone, is responsible for many of the ills linked to the aging process in men. Older men tend to have more bodyfat, and more bodyfat means more aromatase activity and more estrogen. While there is only one known androgen cell receptor, estrogen has two: estrogen receptor alpha (ERA) and estrogen receptor beta (ERB). Androgens reduce the production of ERB, which in turn blunts the activity of GLUT4, a vital glucose transporter protein, in muscle. A loss of GLUT4 activity can increase insulin resistance and obesity, and when testosterone recedes, ERB activity increases. In addition, having lower testosterone leads to having more visceral, or deep-lying, abdominal fat, which is most unhealthful. Unlike subcutaneous fat, which remains in one place, visceral fat is constantly released into the blood, where it’s transported to the liver. There it makes mischief as a prime cause of the metabolic syndrome, cardiovascular disease, high blood pressure and diabetes. Visceral fat is also rich in aromatase.

Some researchers suggest that because of the metabolic problem discussed above, routine use of aromatase-inhibiting drugs should be considered a sensible treatment for men who have higher estrogen and lower testosterone. Other researchers, however, point to the effects of a total lack of aromatase in animals bred to lack genes that produce it or humans born without the same genes. Aromatase-knockout mice, as they’re called, have twice as much bodyfat as their normal littermates. They also accumulate excess fat in their livers, a condition that is corrected if they receive estrogen. They have resting insulin three times greater than other mice. Human beings who lack aromatase have similar conditions, including higher glucose, insulin and total and low-density lipoprotein, which places them at risk for cardiovascular disease. The abnormalities are all reversed in men who are given estrogen.

How that relates to those who use drugs that interfere with estrogen activity becomes clear when you consider that labels on over-the-counter versions of aromatase inhibitors always warn users not to take them all the time. That’s good advice. None of the supplements completely knock out estrogen. A study³ of young men given one milligram daily of Arimidex, which is far more potent than any over-the-counter estrogen blocker, for 10 weeks found a 50 percent reduction in estradiol, the most active form of estrogen. When you block estrogen in men, you get a reciprocal increase in testosterone. Taking Arimidex caused a slight rise in testosterone in the young men, but in older men who were low in testosterone, taking the same drug in the same dose normalized testosterone. So the effect on testosterone depends on how much your body is making in the first place. As we’ve seen, because estrogen also increases SHBG and ties up testosterone in the blood, lowering estrogen boosts free, or active, testosterone by blunting SHBG production in the liver.

A higher count of free testosterone, however, comes with a price. Estrogen-blocking supplements don’t affect another enzyme, 5-alpha reductase, which converts free testosterone into dihydrotestosterone, the hormone linked to male-pattern baldness, acne and prostate disease. So in effect, you are trading one set of problems (high estrogen) for another (high DHT). The effect isn’t significant enough to cause problems with short-term use, but not getting off such supplements periodically could present some real problems.

References

¹ Karila, T.A.M., et al. (2008). Rapid weight loss decreases serum testosterone. Int J Sports Med. 29(11):872-7.

² Tomaszewski, M., et al. (2008). Association between lipid profile and circulating concentrations of estrogens in young men. Atheroscl. In press.

³ Mauras, N., et al. (2000). Estrogen suppression in males: metabolic effects. J Clin Endocrin Metabol. 85:2370-2377.

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

  

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Nitric Oxide: A New Source to Pump You Up by Jerry Brainum

Nitric oxide supplements are hot in the bodybuilding supplement world. Most are based on the amino acid arginine, which is the immediate precursor of nitric oxide synthesis in the body. How much arginine converts to NO depends on several factors, including enzyme activity. Another factor is how much arginine gets absorbed into the body. Taking large doses of oral arginine increases the activity of an enzyme in the liver called arginase, which breaks down arginine, thus blunting it’s uptake into the blood.

Some studies show that you need 18 grams or more for arginine to be effectively converted into NO. In contrast most NO supplements contain a modest dose of three to four grams. The larger doses of arginine require intravenous infusion to bypass the arginase barrier in the liver. Attempting to swallow 12 grams of arginine or more at a time usually results in nausea. That’s probably why most NO supplements contain smaller doses.

Several studies have shown that some bodybuilders who’ve used NO supplements experience symptoms indicating excess NO production in the body. One typical side effect is a drop in blood pressure, since NO widens, or dilates, blood vessels. Though it may not be welcome, it does show that the NO supplements are working as advertised. Other studies, however, show that no oral dose of arginine has any effect on blood vessels. As researcher Richard Bloomer, Ph.D., has pointed out, you wouldn’t want a huge sudden release of NO. Excess amounts are implicated in septic shock—sometimes called blood poisoning—which has a 50 percent mortality rate. Keep in mind that NO is a double-edged biochemical sword. It’s a free radical, which, when combined with hydrogen peroxide released during normal metabolism, becomes peroxinitrate, one of the more potent and damaging free radicals.

NO offers vital benefits besides the well-known expansion of blood vessels. Studies show that NO generation in the heart is involved in important cell-signaling reactions. In the brain NO regulates transmissions across neurons. It’s also involved in release of hormones, including both testosterone and growth hormone. Various diseases have a characteristic NO deficiency—for example diabetes, high blood pressure and pulmonary hypertension.
The most popular method for increasing NO is through the use of Viagra, which lowers blood pressure. Diabetics, who often lack NO, don’t respond as well to Viagra. Nitric oxide combined with vitamin B12 is proving effective for treating dogs that have cancer. The B12 disguises the NO, enabling it to penetrate and destroy tumors through its free-radical action.

Arginine is not the only means of boosting NO synthesis. Another type of supplement combines L-carnitine with propionate, a salt compound, and the amino acid glycine. Taking 4.5 grams of it daily boosts NO by an average of 18 percent. Taking antioxidants also protects against the premature breakdown of NO in the blood.

Perhaps the most overlooked method of boosting NO is also the cheapest and most available—eating vegetables. Why would vegetables boost NO synthesis? They naturally contain nitrate and nitrites, which are the end products of NO metabolism. While they’re usually inert, the body can recycle them into active NO. The best nitrate-rich foods include lettuce, spinach, beetroot and pomegranate. Another option is to drink vegetable juices. Those foods supply a sustained-release alternative to taking large doses of arginine and may prove helpful to those who have defects in the enzymes that convert arginine into NO.

www.JerryBrainum.com

Butler, A.R.,et al. (2008). Therapeutic uses of inorganic nitrite and nitrate: From the past to the future. Circulation. 117:2151-2159.

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

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See Jerry's book at  http://www.jerrybrainum.com