Written by Dan Gwartney, M.D.
13 September 2011

Olympia Fat-Loss Stack

 

 

In this month’s ‘Testosterone’ column, many of the anabolic agents used to create extreme muscular hypertrophy are discussed— the ‘Olympia Anabolic Stack.’ This article refers to the agents used to pare down subcutaneous body fat to absolute minimal levels. The mechanisms used to achieve this goal are as varied as they are for building muscle bulk and include familiar, as well as exotic, options.

As stated in the ‘Olympia Anabolic Stack,’ this discussion is meant to illuminate some of the happenings in the shadows; it does not condone, support, or imply these agents can be used safely or legally as described. It also does not minimize the efforts and discipline of the professional bodybuilder, nor should it debase the socially-positive motivation these men provide to their fans and the public.

Fat loss is a goal that has escaped most Americans, as the rates of obesity escalate. Yet, for decades, bodybuilders of all races and nationalities have demonstrated that it is possible to achieve body fat percentages in the low-to-mid single digits. The disparity between the burgeoning midline of the public versus the lean abdomens of the Olympians begs for an explanation, in the hope that the experiences of these men might open therapeutic avenues of research. Sadly, the politics involved and social stigma attached to the exhibition sport of bodybuilding impedes any such melding.

The basis for reaching a non-age adjusted body fat percentage of 3 percent or less is founded first and foremost on disciplined dieting. Nobody gets lean without controlling their calorie intake— regardless of drugs, surgery, and exercise. Contestants on the television reality show “The Biggest Loser” lost tremendous amounts of weight in a relatively short period; sadly, the producers focused on the more exciting exercise routines and emotional drama rather than the boring diet plans.

Exercise is no chump-change player when it comes to fat loss, and professional bodybuilders know it well. They typically exercise from 75 to 180 minutes a day, if one includes posing and morning low-intensity cardio as part of their exercise regimen.

One needs to bear in mind that the extreme amount of skeletal muscle developed places an equivalent metabolic demand. Sports commentators were in awe of Olympic swimmer Michael Phelps’ reported daily intake of roughly 10,000 calories, which he managed to burn through the many hours of swimming, aided by his youthful metabolism. Professional bodybuilders may consume 4,000 to 5,000 calories a day at various phases of contest preparation. Obviously, as they close on the contest date, bodybuilders pare those calories down and manipulate the macronutrient intake. During the last few days leading up to a show, a 260-pound bodybuilder may reduce his calories down to 1,300 to 1,500; some continue to consume as many as 3,000 or more.

Many recreational athletes diet and train with similar intensity and discipline, but fail to come even close to the ‘peeled’ appearance of the Olympia contestants. The difference lies in genetics and drugs. People need to remember that these men represent the ‘best of the best’ in those departments. The ability to respond to the conditions applied to the body (diet, training, drugs, etc.) depends heavily on the individual’s unique genetic predisposition.1 The role of genes as the final determinant of potential makes the allure of gene-doping almost irresistible for elite athletes in all sports, something the World Anti-Doping Agency is already preparing to face.2

As of now, there is no documented or proven way to buy new physique-enhancing genes in humans. Every year, some adolescent television comedy dusts off the worn-out line, “You can’t pick your parents, but you can pick your nose.” In a few years, gene doping may change that— hopefully retiring that tired punchline.

In the absence of having perfect genes, aspiring titans resort to drugs to trigger metabolic reactions. In bodybuilding, the desired reactions are increasing muscle size and decreasing subcutaneous fat and total fat mass.

‘Tried-and-True’ Drugs for Fat Loss

As with anabolic agents, there are ‘tried-and-true’ drugs that are used almost universally among bodybuilders, and others that are less well known due to the secretive and competitive nature of the culture. Surprisingly, few bodybuilders use prescription fat-loss drugs. This is because most approved prescription weight-management drugs rely on appetite suppression or reducing nutrient absorption.3 Non-specific weight loss reduces lean mass as well, a detriment to size and strength. Bodybuilders are focused on building and maintaining muscular mass— a catabolic, hypocaloric diet would harm their chances at competitive success.

Instead, bodybuilders look for drugs that accelerate the metabolic rate, increase thermogenesis, affect nutrient partitioning, stimulate lipolysis, reduce adipocyte differentiation or survival, or reduce extracellular water.

Obesity is not a 21st-century condition. Physicians, shamans, and pitchmen have been offering ‘cures’ for obesity for centuries. Among the early treatments was organ consumption, specifically eating thyroid tissue from pigs, cattle, etc.4 Thyroid hormone regulates the rate at which nutrient-based substrates (calories) are shuttled through the mitochondria to generate heat and ATP— cellular energy. People suffering from thyroid disorders (low concentrations of active thyroid hormone) tend to be easily fatigued, intolerant to cold, and gain weight. Conversely, conditions of excess result in weakness, tremors, insomnia, intolerance to heat, and weight loss. This weight loss is generic, not specific to adipocytes— resulting in the loss of skeletal muscle mass, as well as body fat.

Of course, a bodybuilder using a variety of anabolic drugs is protected against the muscle-wasting effects of hyperthyroidism, but obese patients prescribed supraphysiologic dosages of thyroid often demonstrate weakness and loss of lean mass.5 Among bodybuilders, the favored drug is Cytomel— synthetic T3 which is many times more active than the commonly-prescribed Synthroid (levothyroxine— T4).6 Other thyroid hormone analogs exist, but none have shown sufficient specificity for fat loss to be used in the treatment of obesity. The risk of heart rhythm disturbances has caused this therapy to fall into disfavor.

Also embedded in ancient practices of more primitive cultures is the use of ephedrine and similar compounds.7 Originally sourced from plants, ephedrine and related alkaloids increase the sympathetic state of an individual. Sympathetic tone refers to the balance of excitement versus relaxation from the point of view of the nervous system. When sympathetic tone is elevated, such as when one takes ephedrine/caffeine, the body acts as though it is on high alert— the ‘fight or flight’ mechanism.

During such events, whether caused by immediate danger or a chemical stimulus, adrenaline and adrenaline-like chemicals flood the receptors on the muscles, fat cells, brain, liver, etc. The net result is increased muscle rigidity and activity, greater calorie burning, fat release from fat cells, and generally a reduction in appetite.

This class of drugs, called sympathomimetics, also has the added benefits of reducing fatigue perception, increasing force generation, boosting alertness and pep, lowering the perceived need for sleep, and improving certain mental/cognitive functions. Generally safe, they carry a risk of tremors, emotional irritability, irregular heartbeat, insomnia, high blood pressure, etc.8

Ephedrine and caffeine in combination remains very popular, even with the restrictions against ephedrine/pseudoephedrine purchase. These two chemicals can be used in the production of methamphetamine.9 There is certainly good reason for ephedrine/caffeine’s popularity— it is very effective and does not impair performance or muscular growth.10 In fact, it may even aid in building strength and size to a slight degree.

More potent drugs exist for stimulating the beta-adrenergic pathway, including asthma medications. It is interesting how many Olympic athletes, Tour de France cyclists, etc. are being treated for ‘asthma.’11 Beta-agonist inhalers expand the airways, allowing performance athletes to breathe easier and resist fatigue. Used chronically, certain beta-agonists can stimulate receptors on the fat cell to release stored fat, and simultaneously stimulate skeletal muscle to increase the rate and percentage of fat calories burned, even at rest.

Clenbuterol, GH, and Sodium Depletion

The reigning king in this category is clenbuterol. The downside to clenbuterol is that it rapidly loses effectiveness due to receptor downregulation, necessitating a near day-to-day cycling of the drug.12 Further, side effects including tremor, nervousness, irregular heartbeat, and other conditions may emerge at the dose required for significant effect.13 Surprisingly, there has not been much in the way of novel agents in this drug category, with the exception of formoterolol, which does not have sufficient reported experience to comment upon, relative to illicit fat-loss use.

Still rooted in the early years of the prior century, one comes across the story of 2,4-dinitrophenol (DNP) as a weight-loss drug.14 According to reports, workers exposed to DNP dust in munitions factories, pesticide manufacturing, etc., were experiencing weight loss, easy fatigue, fever, and death.15 It was discovered that this chemical is capable of easily traversing the membrane barrier of the mitochondria (the part of a cell where energy in the form of ATP is produced), uncoupling calorie burning from energy production.16 In very small, measured doses, DNP can accelerate fat loss by ramping up calorie burning by 30 percent or greater (resting energy expenditure), but at the cost of generating a tremendous heat burden and oxidative damage.

Forewarned of the historical risk associated with this chemical and the recent deaths in young adults using the drug for bodybuilding or weight-loss purposes, many professionals are still using DNP from time to time.17 It is relatively easy to spot the chronic DNP user, with characteristic breath and a yellowish tinge to the complexion that is different from the yellowing caused by jaundice.

Human growth hormone (GH) was originally viewed as an anabolic drug, due in part to its role in the growth and development of children, and its defining name. However, as most professionals of the mid-to-late 1980s to mid-1990s learned, at anabolic concentrations in adults, it causes a variety of disfiguring and potentially harmful side effects. However, and fortunately for aging adults, at a lower dose (2-3 IU/day), GH can still provide significant fat-loss effect and aid in soft tissue recovery.18 The fat-loss effect of GH occurs at the level of the fat cell, but care needs to be taken— as exceeding the marginal dose can induce insulin resistance/glucose intolerance (pre-diabetes), and stimulates the liver to pump glucose into the bloodstream.

There is a little-explored path in the fat cell that involves cortisol and estrogen. Two enzymes are present in the fat cell, 11beta-HSD and aromatase. 11beta-HSD activates cortisol in fat cells. High intracellular cortisol levels increase the conversion of testosterone to estradiol (estrogen).19 By using aromatase inhibitors, bodybuilders reduce the fat storage-promoting increase of estrogen, secondary to supraphysiologic anabolic steroid use. The primitive drug, Cytadren (aminoglutethimide), was originally used by bodybuilders to lower cortisol levels, but aminoglutethimide is a non-specific drug that blocks production of several steroid hormones, including estrogen.20

Fat cells are derived from the same precursor cells as muscle. It may not surprise some to learn that androgenic anabolic steroids divert these precursor cells from becoming fat cells to skeletal muscle differentiation.21 Some might think it would require a particularly potent steroid, such as trenbolone or oxymetholone, but the effect is seen with elevated testosterone concentration. There are no reports of bodybuilders using other drugs to alter the balance of precursor cell differentiation, perhaps due to the ability of bodybuilders to achieve near-absolute ‘leanness.’

It is important to acknowledge the role of diuretics in bodybuilding. Bodybuilders utilize carbohydrate depletion-loading to increase intracellular water, along with synthol or related site-enhancement drugs. Sodium depletion, drinking distilled water, etc., are tools of the drug-free athlete. For the top pros, the more predictable and potent powers of diuretics are used. The ‘big daddy’ is Bumex (bumetanide), but many use spironolactone in conjunction, to preserve potassium.22 The risk involved with diuretics is serious, and likely account for some of the episodes of relentless cramping and heart palpitations that have been witnessed. Diuretics may also have played a role in the competition-associated deaths that have occurred in professional bodybuilding.23

The Pinnacle of Fat Loss?

Bodybuilders have reached the pinnacle of fat loss— for the most part. Timed correctly, the top amateur and professional competitors can present themselves with such low levels of subcutaneous body fat that cross-striations and vascularity are evident from 10 rows back— even at rest. This success keeps the demand for more potent fat-reducing techniques low. Thus, there are no reliable reports of bodybuilders seeking out anti-sense therapy, or even mesotherapy to gain an advantage. It is possible that someone has sought out some exotic therapy or surgical technique, but for the most part, bodybuilders are much more interested in experimenting with anabolic drugs/biologics— as any additional competitive advantage in fat loss would be minimal.

References:
1. Santiago C, Ruiz JR, et al. Does the polygenic profile determine the potential for becoming a world-class athlete? Insights from the sport of rowing. Scand J Med Sci Sports 2009 Apr 20. [Epub ahead of print]
2. Baoutina A, Alexander IE, et al. Developing strategies for detection of gene doping. J Gene Med 2008 Jan;10(1):3-20.
3. Sullivan AC, Comai K. Pharmacological treatment of obesity. Int J Obes 1978;2(2):167-89.
4. Hedberg CW, Fishbein DB, et al. An outbreak of thyrotoxicosis caused by the consumption of bovine thyroid gland in ground beef. N Engl J Med 1987 Apr 16;316(16):993-8.

5. Brick JE, Brick JF, et al. Musculoskeletal disorders. When are they caused by hormone imbalance? Postgrad Med 1991 Nov 1;90(6):129-32, 135-6.

5. Brick JE, Brick JF, et al. Musculoskeletal disorders. When are they caused by hormone imbalance? Postgrad Med 1991 Nov 1;90(6):129-32, 135-6.
6. Wiersinga WM. Thyroid hormone replacement therapy. Horm Res 2001;56 Suppl 1:74-81.
7. Fleming RM. Safety of ephedra and related anorexic medications. Expert Opin Drug Saf 2008 Nov;7(6):749-59.
8. Hallas J, Bjerrum L, et al. Use of a prescribed ephedrine/caffeine combination and the risk of serious cardiovascular events: a registry-based case-crossover study. Am J Epidemiol 2008 Oct 15;168(8):966-73.
9. Cunningham JK, Liu LM. Impacts of federal precursor chemical regulations on methamphetamine arrests. Addiction. 2005 Apr;100(4):479-88.
10. Magkos F, Kavouras SA. Caffeine and ephedrine: physiological, metabolic and performance-enhancing effects. Sports Med 2004;34(13):871-89.
11.Tsitsimpikou C, Tsiokanos A, et al. Medication use by athletes at the Athens 2004 Summer Olympic Games. Clin J Sport Med 2009 Jan;19(1):33-8.
12. Huang H, Gazzola C, et al. Differential effects of dexamethasone and clenbuterol on rat growth and on beta2-adrenoceptors in lung and skeletal muscle. J Anim Sci 2000 Mar;78(3):604-8.
13. van der Kuy PH, Stegeman A, et al. Falsification of Thai dianabol. Pharm World Sci 1997 Aug;19(4):208-9.
14. Judah JD. The action of 2:4-dinitrophenol on oxidative phosphorylation. Biochem J. 1951 Aug;49(3):271-85.
15. Colman E. Dinitrophenol and obesity: an early twentieth-century regulatory dilemma. Regul Toxicol Pharmacol 2007 Jul;48(2):115-7.
16. Blaikie FH, Brown SE, et al. Targeting dinitrophenol to mitochondria: limitations to the development of a self-limiting mitochondrial protonophore. Biosci Rep 2006 Jun;26(3):231-43.
17. Miranda EJ, McIntyre IM, et al. Two deaths attributed to the use of 2,4-dinitrophenol. J Anal Toxicol 2006 Apr;30(3):219-22.
18. Bengtsson BA, Brummer RJ, et al. Growth hormone and body composition. Horm Res 1990;33 Suppl 4:19-24.
19. Bélanger C, Luu-The V, et al. Adipose tissue intracrinology: potential importance of local androgen/estrogen metabolism in the regulation of adiposity. Horm Metab Res 2002 Nov-Dec;34(11-12):737-45.
20. Igaz P, Tömböl Z, et al. Steroid biosynthesis inhibitors in the therapy of hypercortisolism: theory and practice. Curr Med Chem 2008;15(26):2734-47.
21. Blouin K, Veilleux A, et al. Androgen metabolism in adipose tissue: recent advances. Mol Cell Endocrinol 2009 Mar 25;301(1-2):97-103.
22. al-Zaki T, Taibot-Stern J. A bodybuilder with diuretic abuse presenting with symptomatic hypotension and hyperkalemia. Am J Emerg Med 1996 Jan;14(1):96-8.
23. Furlanello F, Serdoz LV, et al. Illicit drugs and cardiac arrhythmias in athletes. Eur J Cardiovasc Prev Rehabil 2007 Aug;14(4):487-94.

References:
1. Santiago C, Ruiz JR, et al. Does the polygenic profile determine the potential for becoming a world-class athlete? Insights from the sport of rowing. Scand J Med Sci Sports 2009 Apr 20. [Epub ahead of print]
2. Baoutina A, Alexander IE, et al. Developing strategies for detection of gene doping. J Gene Med 2008 Jan;10(1):3-20.
3. Sullivan AC, Comai K. Pharmacological treatment of obesity. Int J Obes 1978;2(2):167-89.
4. Hedberg CW, Fishbein DB, et al. An outbreak of thyrotoxicosis caused by the consumption of bovine thyroid gland in ground beef. N Engl J Med 1987 Apr 16;316(16):993-8.

5. Brick JE, Brick JF, et al. Musculoskeletal disorders. When are they caused by hormone imbalance? Postgrad Med 1991 Nov 1;90(6):129-32, 135-6.
6. Wiersinga WM. Thyroid hormone replacement therapy. Horm Res 2001;56 Suppl 1:74-81.
7. Fleming RM. Safety of ephedra and related anorexic medications. Expert Opin Drug Saf 2008 Nov;7(6):749-59.
8. Hallas J, Bjerrum L, et al. Use of a prescribed ephedrine/caffeine combination and the risk of serious cardiovascular events: a registry-based case-crossover study. Am J Epidemiol 2008 Oct 15;168(8):966-73.
9. Cunningham JK, Liu LM. Impacts of federal precursor chemical regulations on methamphetamine arrests. Addiction. 2005 Apr;100(4):479-88.
10. Magkos F, Kavouras SA. Caffeine and ephedrine: physiological, metabolic and performance-enhancing effects. Sports Med 2004;34(13):871-89.
11.Tsitsimpikou C, Tsiokanos A, et al. Medication use by athletes at the Athens 2004 Summer Olympic Games. Clin J Sport Med 2009 Jan;19(1):33-8.
12. Huang H, Gazzola C, et al. Differential effects of dexamethasone and clenbuterol on rat growth and on beta2-adrenoceptors in lung and skeletal muscle. J Anim Sci 2000 Mar;78(3):604-8.
13. van der Kuy PH, Stegeman A, et al. Falsification of Thai dianabol. Pharm World Sci 1997 Aug;19(4):208-9.
14. Judah JD. The action of 2:4-dinitrophenol on oxidative phosphorylation. Biochem J. 1951 Aug;49(3):271-85.
15. Colman E. Dinitrophenol and obesity: an early twentieth-century regulatory dilemma. Regul Toxicol Pharmacol 2007 Jul;48(2):115-7.
16. Blaikie FH, Brown SE, et al. Targeting dinitrophenol to mitochondria: limitations to the development of a self-limiting mitochondrial protonophore. Biosci Rep 2006 Jun;26(3):231-43.
17. Miranda EJ, McIntyre IM, et al. Two deaths attributed to the use of 2,4-dinitrophenol. J Anal Toxicol 2006 Apr;30(3):219-22.
18. Bengtsson BA, Brummer RJ, et al. Growth hormone and body composition. Horm Res 1990;33 Suppl 4:19-24.
19. Bélanger C, Luu-The V, et al. Adipose tissue intracrinology: potential importance of local androgen/estrogen metabolism in the regulation of adiposity. Horm Metab Res 2002 Nov-Dec;34(11-12):737-45.
20. Igaz P, Tömböl Z, et al. Steroid biosynthesis inhibitors in the therapy of hypercortisolism: theory and practice. Curr Med Chem 2008;15(26):2734-47.
21. Blouin K, Veilleux A, et al. Androgen metabolism in adipose tissue: recent advances. Mol Cell Endocrinol 2009 Mar 25;301(1-2):97-103.
22. al-Zaki T, Taibot-Stern J. A bodybuilder with diuretic abuse presenting with symptomatic hypotension and hyperkalemia. Am J Emerg Med 1996 Jan;14(1):96-8.
23. Furlanello F, Serdoz LV, et al. Illicit drugs and cardiac arrhythmias in athletes. Eur J Cardiovasc Prev Rehabil 2007 Aug;14(4):487-94.