Life is balance. The teeter-totter on school playgrounds is a perfect example of how things tend to gravitate toward equilibrium unless some outside force acts. A pair of equal-weight first-grade children would soon get bored and wander off unless they start leg pressing the teeter-totter up and down in alternate fashion. However, when the recess bell rings and all the students have scampered back into class, the teeter-totter wobbles back into the neutral position.
Physiology is much like that teeter-totter, despite all the efforts of mankind. Unless there are abnormal conditions (e.g., famine, infection, cancer), creatures tend to approximate the average of their respective species. Of course, mankind has tossed all the rules out the window, with Western societies living in very unnatural environments. This has resulted in over-representation of the extremes and broad deviations from the “average” when plotting common measurements such as height and weight. Take the clear example of childhood obesity, which is not defined by an agreed upon concrete BMI (body mass index) or body fat percentage. Children are considered overweight if their weight is greater than the 95th percentile and at-risk for overweight if they are between the 85th and 95th percentiles by the Centers for [FONT=tahoma, verdana, geneva, lucida, lucida grande, arial, helvetica, sans-serif]Disease Control[/FONT] and Prevention in the United States. In Europe, they are more clear, calling children over the 95th percentile obese and those called “at risk” in the U.S. overweight. Theoretically, only 5 percent of children should be obese and no more than 10 percent overweight. Yet, the prevalence for childhood overweight/obesity is 25 percent and 11 percent in the U.S. This means more than one-third of children are starting life with a weight-management problem, over twice the “defined” amount.
Overweight/obesity management does not get better with age, it actually gets worse. As the body matures and the wild hormonal swings of adolescence stabilize, the body seeks to regain equilibrium. Unfortunately, if it is forced to do so in an unnatural environment or condition, it does so by shifting its metabolic/hormonal balance. Next time you are in the airport, look at the people carrying a heavy suitcase. They balance their posture by leaning their upper body to the side opposite the luggage. Now, imagine a person carrying one piece of heavy luggage in the same hand all his life. Eventually, he would suffer joint problems, back pain and have a strange gait (walk).
Excess weight not only is unhealthy due to the structural demands it places on the body, but also because of metabolic imbalances it creates. These imbalances involve a number of systems, affecting every organ in the body over time. One clear example is the androgen status of a person. Fat is not a metabolically quiet tissue; it is active and secretes hormones and factors that alter the metabolism of other tissues and the physiology of the individual. Further, the state of being overfed also alters the normal swing between hunger and satiety (fullness) that provides a rhythm in the peripheral tissues and the brain, as energy stores are monitored and managed. If a person is also habitually sedentary (a couch potato), then the absence of signals from working muscle, as well as decreased disposal of nutrients from the blood (sugar, fatty acids, amino acids, etc.) compounds the problem to an even greater degree.
Central obesity, characterized by the “apple shape” or a “beer belly,” is associated with low total testosterone. Aging, obesity, prolonged immobilization and other states that are associated with an elevated fat mass tend to have lower total testosterone concentrations than seen in healthy, active, normal-weight males.
Understanding these relationships cause one to be perplexed on the surface when confronted with the revelations elegantly reviewed in an article recently published in the journal Nutrition Reviews. Researchers from Laval University in Quebec City, Canada, summarized the effects of weight loss due to hypocaloric dieting on the androgen status of men and women. Though the effects were more pronounced in women, the conclusion held true for men as well. In a state of weight loss due to reduced food intake, bioavailable testosterone was reduced as well.
Bioavailable testosterone refers to testosterone that either circulates freely in the bloodstream or is loosely bound (held) by the nonspecific protein-carrier, albumin. Testosterone in these two states (free or albumin-bound) can easily pass into target tissue, such as skeletal muscle, and interact with intra-cytoplasmic receptors and co-regulators to affect changes (the albumin-bound testosterone “breaks free” first). In the muscle, this means free and albumin-bound testosterone are primarily responsible for the androgen-related muscle hypertrophy. The contrasting state is testosterone bound to the more specific protein-carrier called “sex hormone-binding globulin” (SHBG). SHBG-bound testosterone is considered to be “unavailable” to cause changes in androgen-sensitive tissue, such as muscle. This is not entirely correct, as it is believed that SHBG-bound testosterone, as well as albumin-bound testosterone, may interact with androgen receptors in cell membranes. The quick responses of these membrane-bound receptors are called nongenomic, as they do not travel to the nucleus of the cell (where the DNA lies). Instead, the nongenomic receptor responses take place at or near the membrane, changing the activity of enzyme pathways that trigger anabolic cell functions.
In the Nutrition Reviews article, the observation was that people who lose weight by following a hypocaloric diet experienced an increase in SHBG while total androgen concentration did not change. It was noted that the type of diet followed (low-fat, low-carb, etc.) did not affect the effect of weight loss on androgen status. This implies that people who are actively losing weight experience a reduction in free and bioavailable testosterone. This is consistent with previous studies that show a decrease in SHBG in men in association with weight gain. This finding is not a real surprise if one considers the everyday experience of dieters or more specifically, those of athletes/bodybuilders who are cutting weight to meet a weight-class restriction or to get “ripped” for competition. Dropping calories below maintenance is subjectively associated with a marked lowering of 1-rep max and loss of lean body mass. Many athletes combat this by depending more heavily upon ergogenic aids (e.g., supplements, stimulants, anabolic drugs). For the drug-free athlete, there are a few strategies that can ameliorate the weight-loss induced decrease in bioavailable testosterone. Focusing on hypertrophy-oriented lifting (higher volume, shorter rest) induces a greater spike in testosterone (and cortisol) than powerlifting schemes. The protocol followed in one study showing this using salivary testosterone (and cortisol) was 10 sets of 10 reps with 2-minute breaks between sets. Also, while the media focuses on the “bacon and eggs” component of Atkins-like diets, including a significant amount of carbohydrates, poly- and mono-unsaturated fats will help maintain total testosterone. Zinc, magnesium and other micronutrients may also aid in maintaining androgen status, particularly for those who follow diets with narrowly defined food choices.
The interesting tangent to the relationship between weight loss and androgen status is defining the relationship. Is hypocaloric weight loss the cause of reduced bioavailable testosterone, or does an abnormal ratio of bioavailable to SHBG-bound testosterone support the growth of fat mass? During weight loss, adipocytes release stored fats from triglyceride vacuoles. These vacuoles are like oil droplets in water. Unfortunately, these vacuoles may have held not only stored fat, but also fat-soluble environmental pollutants. Endocrine disruptors are chemicals present in the air or water, commonly released from industrial sources. The chemical bisphenol A that is present in certain plastics is one example that has been in the news recently. Bisphenol A exposure is postulated to increase the risk of numerous cognitive, reproductive and metabolic problems, in part, through its agonistic actions at the estrogen receptor (ER-alpha). Estradiol, the natural estrogen produced as a metabolite of testosterone, increases SHBG production.
Elevations in bioavailable testosterone could be a protective adaptation to early weight gain, as testosterone reduces the proliferation of fat cells from stem cell reserves and activates the breakdown and release of stored fat. If fat gain goes unchecked though, the fat cells are capable of inactivating testosterone and converting it into estradiol to promote the further storage of fat and growth of new fat cells. The binding of bioavailable testosterone to the sequestered (hidden away) SHBG-bound testosterone may be a physiologic adaptation to encourage the return to a normal weight and release further stored fat to provide energy during a period of relative starvation. Increasing the SHBG-bound component of testosterone during weight loss may allow for fat cell proliferation and prevent the development of hypertrophic adipocytes (fat cells) which are associated with many of the metabolic problems of obesity.
These simple observations and thoughts do not begin to touch upon the complexity of these findings, as the actions of other tissues and hormones that are affected by the relative energy stores (fat) have not been addressed. Adipokines, leptin, ghrelin, insulin sensitivity, etc., all combine to harmonize in the hormonal orchestra of human metabolism. When one section is out of tune, it is inevitable that the symphony is ruined regardless how much louder the rest of the orchestra plays.
Obesity is an imbalance between a person and his environment. In some cases, it is an inevitable consequence of a genetic error in coding. In most cases, it is the consequence of the body being forced to accommodate illogical or unnatural conditions. In response to obesity and attempts to return to normal weight, changes occur, including changes in the endocrine system. Androgens, including testosterone, are potent anabolic hormones that dictate the function of many tissues and are regulated in response to physiologic conditions. When food supply is low, bioavailable testosterone is decreased to reduce the demands for protein and other nutrients during food shortages. For the athlete, the consequence may be a loss of strength or lean mass. It is possible that testosterone concentrations, particularly bioavailable testosterone, may be maintained by paying close attention to including specific nutrients (e.g. poly- and mono-unsaturated fats, zinc, magnesium, etc.), but awareness of lessened anabolic support is necessary for the athlete so he/she may tailor their efforts and expectations appropriately.
References:
Dehghan M, Akhtar-Danesh N, et al. Childhood obesity, prevalence and prevention. Nutrition Journal, 2005;4:24. doi:10.1186/1475-2891-4-24
DeClercq V, Taylor C, et al. Adipose tissue: the link between obesity and cardiovascular disease. Cardiovasc Hematol Disord Drug Targets, 2008 Sep;8(3):228-37.
Smith PM, Ferguson AV. Neurophysiology of hunger and satiety. Dev Disabil Res Rev, 2008;14(2):96-104.
Chu LW, Tam S, et al. Serum total and bioavailable testosterone levels, central obesity, and muscle strength changes with aging in healthy Chinese men. J Am Geriatr, Soc 2008 Jul;56(7):1286-91.
Schneider HJ, Sievers C, et al. Prevalence of low male testosterone levels in primary care in Germany: cross-sectional results from the DETECT study. Clin Endocrinol, (Oxf) 2008 Aug 7. [Epub ahead of print]
Morisset AS, Blouin K, et al. Impact of diet and adiposity on circulating levels of sex hormone-binding globulin and androgens. Nutr Rev, 2008;66(9):506-16.
Heinlein CA, Chang C. Androgen receptor (AR) coregulators: an overview. Endocr Rev, 2002 Apr;23(2):175-200.
Michels G, Hoppe UC. Rapid actions of androgens. Front Neuroendocrinol, 2008 May;29(2):182-98.
Mohr BA, Bhasin S, et al. The effect of changes in adiposity on testosterone levels in older men: longitudinal results from the Massachusetts Male Aging Study. Eur J Endocrinol, 2006 Sep;155(3):443-52.
Webster S, Rutt R, et al. Physiological effects of a weight loss regimen practiced by college wrestlers. Med Sci Sports Exerc, 1990 Apr;22(2):229-34.
Crewther B, Cronin J, et al. The salivary testosterone and cortisol response to three loading schemes. J Strength Cond Res, 2008 Jan;22(1):250-5.
Tamimi R, Mucci LA, et al. Testosterone and oestradiol in relation to tobacco smoking, body mass index, energy consumption and nutrient intake among adult men. Eur J Cancer Prev, 2001 Jun;10(3):275-80.
Gromadzka-Ostrowska J. Effects of dietary fat on androgen secretion and metabolism. Reprod Biol, 2006;6 Suppl 2:13-20.
Imbeault P, Chevrier J, et al. Increase in plasma pollutant levels in response to weight loss in humans is related to in vitro subcutaneous adipocyte basal lipolysis. Int J Obes Relat Metab Disord, 2001 Nov;25(11):1585-91.
vom Saal FS, Myers JP. Bisphenol A and risk of metabolic disorders. JAMA, 2008 Sep 17;300(11):1353-5.
Loukovaara M, Carson M, et al. Regulation of sex hormone-binding globulin secretion and gene expression by cycloheximide in vitro. J Steroid Biochem Mol Biol, 1995 Aug;54(3-4):141-6.
Singh R, Artaza JN, et al. Testosterone inhibits adipogenic differentiation in 3T3-L1 cells: nuclear translocation of androgen receptor complex with beta-catenin and T-cell factor 4 may bypass [FONT=tahoma, verdana, geneva, lucida, lucida grande, arial, helvetica, sans-serif]canonical Wnt signaling[/FONT] to down-regulate adipogenic transcription factors. Endocrinology, 2006 Jan;147(1):141-54.
Blouin K, Boivin A, et al. Androgens and body fat distribution. J Steroid Biochem Mol Biol, 2008 Feb;108(3-5):272-80.
Bays HE, Gonzalez-Campoy JM, et al. Pathogenic potential of adipose tissue and metabolic consequences of adipocyte hypertrophy and increased visceral adiposity. Expert Rev Cardiovasc Ther, 2008 Mar;6(3):343-68.
Physiology is much like that teeter-totter, despite all the efforts of mankind. Unless there are abnormal conditions (e.g., famine, infection, cancer), creatures tend to approximate the average of their respective species. Of course, mankind has tossed all the rules out the window, with Western societies living in very unnatural environments. This has resulted in over-representation of the extremes and broad deviations from the “average” when plotting common measurements such as height and weight. Take the clear example of childhood obesity, which is not defined by an agreed upon concrete BMI (body mass index) or body fat percentage. Children are considered overweight if their weight is greater than the 95th percentile and at-risk for overweight if they are between the 85th and 95th percentiles by the Centers for [FONT=tahoma, verdana, geneva, lucida, lucida grande, arial, helvetica, sans-serif]Disease Control[/FONT] and Prevention in the United States. In Europe, they are more clear, calling children over the 95th percentile obese and those called “at risk” in the U.S. overweight. Theoretically, only 5 percent of children should be obese and no more than 10 percent overweight. Yet, the prevalence for childhood overweight/obesity is 25 percent and 11 percent in the U.S. This means more than one-third of children are starting life with a weight-management problem, over twice the “defined” amount.
Overweight/obesity management does not get better with age, it actually gets worse. As the body matures and the wild hormonal swings of adolescence stabilize, the body seeks to regain equilibrium. Unfortunately, if it is forced to do so in an unnatural environment or condition, it does so by shifting its metabolic/hormonal balance. Next time you are in the airport, look at the people carrying a heavy suitcase. They balance their posture by leaning their upper body to the side opposite the luggage. Now, imagine a person carrying one piece of heavy luggage in the same hand all his life. Eventually, he would suffer joint problems, back pain and have a strange gait (walk).
Excess weight not only is unhealthy due to the structural demands it places on the body, but also because of metabolic imbalances it creates. These imbalances involve a number of systems, affecting every organ in the body over time. One clear example is the androgen status of a person. Fat is not a metabolically quiet tissue; it is active and secretes hormones and factors that alter the metabolism of other tissues and the physiology of the individual. Further, the state of being overfed also alters the normal swing between hunger and satiety (fullness) that provides a rhythm in the peripheral tissues and the brain, as energy stores are monitored and managed. If a person is also habitually sedentary (a couch potato), then the absence of signals from working muscle, as well as decreased disposal of nutrients from the blood (sugar, fatty acids, amino acids, etc.) compounds the problem to an even greater degree.
Central obesity, characterized by the “apple shape” or a “beer belly,” is associated with low total testosterone. Aging, obesity, prolonged immobilization and other states that are associated with an elevated fat mass tend to have lower total testosterone concentrations than seen in healthy, active, normal-weight males.
Understanding these relationships cause one to be perplexed on the surface when confronted with the revelations elegantly reviewed in an article recently published in the journal Nutrition Reviews. Researchers from Laval University in Quebec City, Canada, summarized the effects of weight loss due to hypocaloric dieting on the androgen status of men and women. Though the effects were more pronounced in women, the conclusion held true for men as well. In a state of weight loss due to reduced food intake, bioavailable testosterone was reduced as well.
Bioavailable testosterone refers to testosterone that either circulates freely in the bloodstream or is loosely bound (held) by the nonspecific protein-carrier, albumin. Testosterone in these two states (free or albumin-bound) can easily pass into target tissue, such as skeletal muscle, and interact with intra-cytoplasmic receptors and co-regulators to affect changes (the albumin-bound testosterone “breaks free” first). In the muscle, this means free and albumin-bound testosterone are primarily responsible for the androgen-related muscle hypertrophy. The contrasting state is testosterone bound to the more specific protein-carrier called “sex hormone-binding globulin” (SHBG). SHBG-bound testosterone is considered to be “unavailable” to cause changes in androgen-sensitive tissue, such as muscle. This is not entirely correct, as it is believed that SHBG-bound testosterone, as well as albumin-bound testosterone, may interact with androgen receptors in cell membranes. The quick responses of these membrane-bound receptors are called nongenomic, as they do not travel to the nucleus of the cell (where the DNA lies). Instead, the nongenomic receptor responses take place at or near the membrane, changing the activity of enzyme pathways that trigger anabolic cell functions.
In the Nutrition Reviews article, the observation was that people who lose weight by following a hypocaloric diet experienced an increase in SHBG while total androgen concentration did not change. It was noted that the type of diet followed (low-fat, low-carb, etc.) did not affect the effect of weight loss on androgen status. This implies that people who are actively losing weight experience a reduction in free and bioavailable testosterone. This is consistent with previous studies that show a decrease in SHBG in men in association with weight gain. This finding is not a real surprise if one considers the everyday experience of dieters or more specifically, those of athletes/bodybuilders who are cutting weight to meet a weight-class restriction or to get “ripped” for competition. Dropping calories below maintenance is subjectively associated with a marked lowering of 1-rep max and loss of lean body mass. Many athletes combat this by depending more heavily upon ergogenic aids (e.g., supplements, stimulants, anabolic drugs). For the drug-free athlete, there are a few strategies that can ameliorate the weight-loss induced decrease in bioavailable testosterone. Focusing on hypertrophy-oriented lifting (higher volume, shorter rest) induces a greater spike in testosterone (and cortisol) than powerlifting schemes. The protocol followed in one study showing this using salivary testosterone (and cortisol) was 10 sets of 10 reps with 2-minute breaks between sets. Also, while the media focuses on the “bacon and eggs” component of Atkins-like diets, including a significant amount of carbohydrates, poly- and mono-unsaturated fats will help maintain total testosterone. Zinc, magnesium and other micronutrients may also aid in maintaining androgen status, particularly for those who follow diets with narrowly defined food choices.
The interesting tangent to the relationship between weight loss and androgen status is defining the relationship. Is hypocaloric weight loss the cause of reduced bioavailable testosterone, or does an abnormal ratio of bioavailable to SHBG-bound testosterone support the growth of fat mass? During weight loss, adipocytes release stored fats from triglyceride vacuoles. These vacuoles are like oil droplets in water. Unfortunately, these vacuoles may have held not only stored fat, but also fat-soluble environmental pollutants. Endocrine disruptors are chemicals present in the air or water, commonly released from industrial sources. The chemical bisphenol A that is present in certain plastics is one example that has been in the news recently. Bisphenol A exposure is postulated to increase the risk of numerous cognitive, reproductive and metabolic problems, in part, through its agonistic actions at the estrogen receptor (ER-alpha). Estradiol, the natural estrogen produced as a metabolite of testosterone, increases SHBG production.
Elevations in bioavailable testosterone could be a protective adaptation to early weight gain, as testosterone reduces the proliferation of fat cells from stem cell reserves and activates the breakdown and release of stored fat. If fat gain goes unchecked though, the fat cells are capable of inactivating testosterone and converting it into estradiol to promote the further storage of fat and growth of new fat cells. The binding of bioavailable testosterone to the sequestered (hidden away) SHBG-bound testosterone may be a physiologic adaptation to encourage the return to a normal weight and release further stored fat to provide energy during a period of relative starvation. Increasing the SHBG-bound component of testosterone during weight loss may allow for fat cell proliferation and prevent the development of hypertrophic adipocytes (fat cells) which are associated with many of the metabolic problems of obesity.
These simple observations and thoughts do not begin to touch upon the complexity of these findings, as the actions of other tissues and hormones that are affected by the relative energy stores (fat) have not been addressed. Adipokines, leptin, ghrelin, insulin sensitivity, etc., all combine to harmonize in the hormonal orchestra of human metabolism. When one section is out of tune, it is inevitable that the symphony is ruined regardless how much louder the rest of the orchestra plays.
Obesity is an imbalance between a person and his environment. In some cases, it is an inevitable consequence of a genetic error in coding. In most cases, it is the consequence of the body being forced to accommodate illogical or unnatural conditions. In response to obesity and attempts to return to normal weight, changes occur, including changes in the endocrine system. Androgens, including testosterone, are potent anabolic hormones that dictate the function of many tissues and are regulated in response to physiologic conditions. When food supply is low, bioavailable testosterone is decreased to reduce the demands for protein and other nutrients during food shortages. For the athlete, the consequence may be a loss of strength or lean mass. It is possible that testosterone concentrations, particularly bioavailable testosterone, may be maintained by paying close attention to including specific nutrients (e.g. poly- and mono-unsaturated fats, zinc, magnesium, etc.), but awareness of lessened anabolic support is necessary for the athlete so he/she may tailor their efforts and expectations appropriately.
References:
Dehghan M, Akhtar-Danesh N, et al. Childhood obesity, prevalence and prevention. Nutrition Journal, 2005;4:24. doi:10.1186/1475-2891-4-24
DeClercq V, Taylor C, et al. Adipose tissue: the link between obesity and cardiovascular disease. Cardiovasc Hematol Disord Drug Targets, 2008 Sep;8(3):228-37.
Smith PM, Ferguson AV. Neurophysiology of hunger and satiety. Dev Disabil Res Rev, 2008;14(2):96-104.
Chu LW, Tam S, et al. Serum total and bioavailable testosterone levels, central obesity, and muscle strength changes with aging in healthy Chinese men. J Am Geriatr, Soc 2008 Jul;56(7):1286-91.
Schneider HJ, Sievers C, et al. Prevalence of low male testosterone levels in primary care in Germany: cross-sectional results from the DETECT study. Clin Endocrinol, (Oxf) 2008 Aug 7. [Epub ahead of print]
Morisset AS, Blouin K, et al. Impact of diet and adiposity on circulating levels of sex hormone-binding globulin and androgens. Nutr Rev, 2008;66(9):506-16.
Heinlein CA, Chang C. Androgen receptor (AR) coregulators: an overview. Endocr Rev, 2002 Apr;23(2):175-200.
Michels G, Hoppe UC. Rapid actions of androgens. Front Neuroendocrinol, 2008 May;29(2):182-98.
Mohr BA, Bhasin S, et al. The effect of changes in adiposity on testosterone levels in older men: longitudinal results from the Massachusetts Male Aging Study. Eur J Endocrinol, 2006 Sep;155(3):443-52.
Webster S, Rutt R, et al. Physiological effects of a weight loss regimen practiced by college wrestlers. Med Sci Sports Exerc, 1990 Apr;22(2):229-34.
Crewther B, Cronin J, et al. The salivary testosterone and cortisol response to three loading schemes. J Strength Cond Res, 2008 Jan;22(1):250-5.
Tamimi R, Mucci LA, et al. Testosterone and oestradiol in relation to tobacco smoking, body mass index, energy consumption and nutrient intake among adult men. Eur J Cancer Prev, 2001 Jun;10(3):275-80.
Gromadzka-Ostrowska J. Effects of dietary fat on androgen secretion and metabolism. Reprod Biol, 2006;6 Suppl 2:13-20.
Imbeault P, Chevrier J, et al. Increase in plasma pollutant levels in response to weight loss in humans is related to in vitro subcutaneous adipocyte basal lipolysis. Int J Obes Relat Metab Disord, 2001 Nov;25(11):1585-91.
vom Saal FS, Myers JP. Bisphenol A and risk of metabolic disorders. JAMA, 2008 Sep 17;300(11):1353-5.
Loukovaara M, Carson M, et al. Regulation of sex hormone-binding globulin secretion and gene expression by cycloheximide in vitro. J Steroid Biochem Mol Biol, 1995 Aug;54(3-4):141-6.
Singh R, Artaza JN, et al. Testosterone inhibits adipogenic differentiation in 3T3-L1 cells: nuclear translocation of androgen receptor complex with beta-catenin and T-cell factor 4 may bypass [FONT=tahoma, verdana, geneva, lucida, lucida grande, arial, helvetica, sans-serif]canonical Wnt signaling[/FONT] to down-regulate adipogenic transcription factors. Endocrinology, 2006 Jan;147(1):141-54.
Blouin K, Boivin A, et al. Androgens and body fat distribution. J Steroid Biochem Mol Biol, 2008 Feb;108(3-5):272-80.
Bays HE, Gonzalez-Campoy JM, et al. Pathogenic potential of adipose tissue and metabolic consequences of adipocyte hypertrophy and increased visceral adiposity. Expert Rev Cardiovasc Ther, 2008 Mar;6(3):343-68.
