Advanced Testosterone Science
By ProSource Product Research Staff | Wednesday, February 21, 2007 12:28:25 PM America/New_York
Test and LH Basics
Testosterone is the principal steroid hormone secreted from specialized cells in the testes (called Leydig cells) in men. Chemically, testosterone is made from cholesterol like all the other steroid hormones. Several hormones stimulate the body's own production of testosterone. The most important and potent stimulator of testosterone secretion is luteinizing hormone (LH), which is secreted from the pituitary gland. In turn LH is stimulated by gonadotropin releasing hormone (GnRH) from the hypothalamus. This regulatory system controlling testosterone is often referred to as the hypothalamic-pituitary-testicular axis. It operates under a classic negative feedback control. When testosterone levels are low, GnRH and LH kick in to stimulate testosterone production. When testosterone is high (which occurs with anabolic steroid use), GNRH and LH are inhibited which shuts down the body's natural production of testosterone. A large portion of testosterone (about 98%) in the circulation is bound to proteins. Roughly half of this is bound tightly to sex hormone biding globulin (SHBG). This reduces the clearance and increases the length time testosterone circulates before being taken up by tissues. The rest of the testosterone is bound to other proteins such as albumin and a small amount (about 2%) exists in the free (unbound) form. It is generally argued that the non-SHBG bound (that is the albumin-bound and free testosterone) is the biologically active portion responsible for the target tissue effects of the steroid. Testosterone acts on most tissues. In skeletal muscle testosterone increases muscle mass primarily by increasing protein synthesis, whereas the effects on protein breakdown are unclear. In adipose tissue, testosterone inhibits lipid uptake and lipoprotein lipase activity, and stimulates lipolysis (fat breakdown) by increasing the number of beta-adrenergic receptors.
In addition to building muscle and breaking down fat, increased testosterone can have favorable effects on a number of other factors including sexual interest, erectile function, mood, and bone density. Hormones elicit cellular effect only if they interact with a specific membrane-bound or nuclear receptor. In the case of testosterone, the hormone must bind to an androgen receptor which exists in many different tissues including skeletal muscle to have any effect on cellular function. Testosterone binding converts the androgen receptor to a transcription factor that can then interact with DNA to regulate androgen-specific gene expression. Muscle hypertrophy is prevented when the androgen receptor is blocked, demonstrating the physiological importance of its presence in skeletal muscle in order to promote muscle accretion.
Factors Affecting Testosterone
Many factors affect the biological activity and target tissue effects of testosterone. For example, testosterone has a diurnal pattern, meaning that levels vary over the day. Testosterone levels peak in the early morning (6:00 to 8:00 am), fall by about 35% during the day reaching a nadir in the early evening, and begin to rise again around midnight. Peak levels in a normal young male are about 22-25 nmol/L and fall to 15-18 nmol/L in the early evening. With aging, the diurnal variation is altered including a decrease in peak testosterone levels and a fall in the frequency and amplitude of LH pulses.
Aging and Obesity
The decline in testosterone usually begins in men in their late thirties and decreases at a relatively constant rate thereafter. There is variation among studies, but the average rate of decline in testosterone is about 1% per year. While testosterone is decreasing, SHBG is increasing as a function of age. This causes an even more profound decline in free testosterone levels on the order of 2-3% per year. The decline in testosterone causes a compensatory rise in LH. There are a number of impairments in the hypothalamic-pituitary-testicular axis that controls testosterone production with aging. Leydig cell number is decreased, there is disruption in LH stimulation of testosterone, and negative feedback loops are more sensitive The prevalence of testosterone deficiency varies somewhat from study to study and the cut-off criteria, but one study reported that almost one-third of men aged 46-89 years had low testosterone (defined as less than 10.4 nmol/L).
Another important determinant of testosterone levels is obesity. Part of the decrease in testosterone with age may be due to the fact obesity increases with age. Testosterone levels are on the order of 25% lower in obese men compared to normal-weight men. It is not just the total testosterone, free testosterone levels are reduced in obesity as well.
Several studies indicate that reducing calories can decrease testosterone levels. Studies in wrestlers, who cut calories and exercise exhaustively to cut weight during the competitive season, have shown dramatic decreases in testosterone. In one study, testosterone levels were measured in wrestlers during the competitive season and again two months after the season. Large reductions in body fat induced by caloric restriction and exercise during the season resulted in the largest decreases in testosterone levels. The wrestlers with an extremely low body fat percentage (less than 5%) demonstrated abnormally low testosterone levels that returned to normal after the season. In another study, testosterone was measured in soldiers who consumed three different levels of energy: 1800, 3200 or 4200 kcal/day all with similar ratios of carbohydrate, protein, and fat. The diets were consumed during 5 days of prolonged exercise and sleep deprivation (4 hrs/day). After 5 days testosterone had decreased by -50% on the low calorie diet and only about -20% on the moderate and high calorie diets. Collectively the studies that have examined the effects of energy intake on testosterone indicate that large reductions in calories and body weight can reduce testosterone levels. This is especially true if a large reduction in calories is combined with prolonged and exhaustive physical activity.
Effect of Exercise on Testosterone
Resistance training has been shown to acutely increase blood concentrations of total testosterone in most studies in men. Resistance exercise-induced elevations in testosterone peak early after exercise and return to baseline by about 60 min post-exercise; pre- and post-exercise meals alter this response. Several factors can influence this rise in testosterone after resistance. Exercises that recruit more muscle mass like the squat elicit a greater increase than exercises that require less muscle tissue. There also appears to be a minimal threshold of volume (sets x reps x weight) in order to increase testosterone levels. Bodybuilding programs (moderate load, high volume, short rest periods) produce greater testosterone responses than powerlifter programs (high-load, low volume, long rest periods). Older individuals have been shown to produce significant elevations of testosterone during an acute bout of resistance exercise, however the absolute concentrations are significantly lower than that of younger individuals. Resistance training not only increases testosterone levels, but also increases the androgen receptor content in muscle, which provides a link to the well characterized adaptations in muscle hypertrophy associated with resistance training.
Feeding and Testosterone
Simply eating affects hormone levels including testosterone. The testosterone response to 800 kcal meals that were either high-fat (57% fat, 9% protein, 34% carbohydrate) or low-fat (1% fat, 26% protein, 73% carbohydrate) was examined in healthy men. Testosterone was not affected after the low-fat meal, but postprandial total and free testosterone concentrations were approximately 30% lower for 4 hr after the high-fat meal. The fat-induced decrease was not related to changes in other steroids (i.e., estrone, estradiol, dihydrotestosterone, LH, percent free testosterone, or sex hormone binding globulin binding capacity). This study indicates fat-rich meals, but not carbohydrate-rich meals, decrease postprandial testosterone levels. Our laboratory has also observed a significant reduction in total testosterone (-22%) and free testosterone (-23%) after a fat-rich meal in healthy men. Another study compared testosterone responses to meals with different sources of protein (soy vs. meat), amounts of fat (lean vs. fatty meat), and sources of fat (animal vs. vegetable). The decrease in testosterone was greater after a low-fat meal consisting of lean meat (-22%) compared to tofu (-15%); a meal consisting of lean meat (-22%) compared to lean meat cooked with animal fat meal (-9%); and a meal consisting of lean meat cooked with vegetable fat (-17%) compared to vegetable oil (-9%).
Although these results do not necessarily agree with the findings mentioned above that only fat-rich meals reduce testosterone, the study does provide further evidence that the composition of meals, particularly the amount and type of fat, influences the circulating testosterone response to meals. All the meals resulted in decreases in testosterone, increases in LH, and no changes in SHBG.
Effect of Feeding on Exercise-Induced Testosterone
Our laboratory showed that a protein and carbohydrate beverage consumed 2 hr before and immediately after a bout of whole body resistance exercise resulted in an increase in testosterone immediately after exercise followed by a sharp decrease to values that were significantly below baseline. In this study, the exact same exercise and supplementation protocol was performed on three consecutive days. The greater reduction in post-exercise testosterone with pre- and post-exercise protein and carbohydrate intake compared to placebo was observed on all three days, emphasizing the consistency and reproducibility of the response.
In another study, the post-exercise testosterone response to supplements containing either protein alone, carbohydrate alone, or a combination of protein and carbohydrate consumed immediately and 2 hr after a bout of resistance exercise in healthy men was examined. In agreement with findings from our study, testosterone had decreased to values below baseline by 30 min post-exercise during all the supplement treatments compared to placebo. Testosterone values remained significantly below baseline 5 to 6 hr whereas testosterone returned to baseline shortly after exercise and stabilized throughout the recovery period. In yet another study, the post-exercise testosterone responses to a mixed meal, an isocaloric beverage of similar nutrient content, and an isocaloric carbohydrate beverage consumed immediately and 2, 4, and 7 hr after exercise was investigated. Compared to a placebo, post-resistance exercise testosterone levels were lower during all the meals at 0.5, 2.5, 4.5 and 8 hr post-exercise. Collectively, these studies indicate that pre- and post-exercise meals decrease post-exercise testosterone levels compared to fasting. The decrease could be due in part to a decrease in the synthesis/secretion of testosterone and/or an increase in metabolic clearance. The decrease in post-exercise testosterone is not associated with a decrease in LH arguing against a decrease in the rate of testosterone secretion, however there could still be a decrease in the testicular responsiveness to LH.
Since post-exercise meals increase muscle-specific protein synthesis during recovery, the lower testosterone levels could be due in part to increased uptake in active skeletal muscle. In support of this hypothesis, recent work in our laboratory has shown that the meal-induced decrease in testosterone after resistance exercise corresponds with an increase in skeletal muscle androgen receptor content measured 60 min after exercise. Our work clearly demonstrated that post-resistance exercise feeding increases androgen receptor content, suggesting increased cellular uptake of testosterone and provides a mechanism for increased protein synthesis found in other studies following post-resistance exercise food intake.
Effect of Habitual Diet on Testosterone: The Diet and Testosterone Link
One way to naturally manipulate testosterone levels is through diet. Of the three macronutrients or energy-providing nutrients in the diet (protein, carbohydrate, and fat) the one shown to affect testosterone to the greatest extent is fat. The scientific literature that has examined the impact of diet on levels of testosterone has focused primarily on manipulation of the percentage of energy derived from fat.
In general, these studies indicate that a diet low in fat is associated with lower testosterone values compared to a diet containing a higher percentage of energy derived from fat. Following is an overview of both cross-sectional and diet intervention studies that have examined the question whether diet impacts testosterone. The majority of cross-sectional studies that have examined the impact of diet on testosterone have involved comparing vegetarians to non-vegetarians or omnivores (meat-eaters). Although vegetarian and non-vegetarian diets differ in many nutrients, a major difference is typically the level of fat. The findings from cross-sectional studies generally indicate that vegetarians have lower testosterone levels compared to omnivores. One study examined the relationship between dietary nutrients and testosterone in men that were either vegetarians or omnivores. The omnivores had 36% higher levels of testosterone compared to the vegetarian men. These differences in testosterone are likely due to differences in diet. The percent calories derived from fat was 34% for the vegetarians and 40% for the omnivores. Also, the vegetarian group consumed significantly more dietary fiber (37 vs. 20 g) and less cholesterol (197 vs. 438 mg) compared to the omnivore group. The omnivore group consumed meat, fish, or poultry 6-7 times per week whereas the vegetarian group did not consume meat. In a similar study the levels of testosterone were compared between men that were vegetarians or omnivores. The omnivores had about 31% higher levels of testosterone compared to the vegetarian men. The percentage of total calories from fat was higher for the omnivores (37%) compared to the vegetarians (30%). The vegetarian group also consumed less cholesterol (296 vs. 524 mg) and saturated fat (27 vs. 43 g) and more fiber (38 vs. 14 g) than the omnivores. The omnivore group consumed animal food regularly whereas the vegetarian group did not consume animal products with the exception of milk and eggs.
The results from diet intervention studies generally agree with the conclusion from cross-sectional studies that low-fat diets are associated with lower testosterone levels than diets higher in fat. One study had male endurance athletes follow a vegetarian diet and a mixed diet each for 6 weeks. Resting testosterone levels were measured after each diet and the testosterone response to a standardized exercise bout was also determined. Resting testosterone levels were 27% higher and post-exercise testosterone was 39% higher on the mixed diet compared to the vegetarian diet. Interestingly, the two diets contained equal percentages of calories derived from protein, carbohydrate, and fat. However the source of protein in the vegetarian diet was derived mainly from vegetable sources (83%) whereas the mixed diet contained significantly less vegetable protein (35%) and more animal protein.
These findings highlight the importance of including animal proteins (e.g., meat, chicken, turkey, fish), or proteins with a full complement of essential amino acids like whey protein, in the diet to optimize resting testosterone levels and testosterone responses to exercise. Another study examined the effect of switching from 2 weeks of a high fat diet (>100 g fat/day) to 2 weeks of a low fat diet (less than 20 g fat/day) on testosterone levels in normal-weight men. After switching from the high-fat to the low-fat diet the free testosterone concentration decreased 21%. Testosterone levels were measured in healthy normal-weight men while consuming their normal diet (40% calories from fat) and then after switching to a diet low in fat (25% calories from fat) for 6 weeks. Compared to the normal-diet (40% fat), testosterone levels decreased by 15% after the low-fat diet period. Similar findings were noted in testosterone levels in healthy men after 3 days of a high-fat diet (60% fat) or a low-fat diet (30%). Testosterone levels were 14% higher after the high-fat diet compared to the low-fat diet. In a different study, testosterone levels in healthy men who consumed a low-fat (19% fat) and a high-fat (41% fat) diet for 10 weeks were compared. Testosterone levels were 15% higher after 10 weeks of the high-fat diet compared to the low-fat diet.
The type of fat also has an affect on testosterone metabolism. Studies indicate that unsaturated fat results in greater testosterone synthesis and secretion into the blood than saturated fat. One study showed that compared to saturated fat, rapseed oil (rich in monounsaturated fat) resulted in higher testosterone levels in the circulation, greater testosterone binding to muscle, and greater synthesis of testosterone in the testes. Other studies have shown that feeding fish oil can cause an increase in testosterone synthesis in animals. The mechanism by which type of fat affects testosterone metabolism is unclear but may work by altering the plasma membrane composition, which in turn may alter the responsiveness of receptors to other testosterone-stimulating hormones like LH.
In summary, the cross-sectional and diet intervention studies indicate that low-fat diets (20-30% of calories) are associated with lower testosterone levels compared to diets higher in fat (about 40% of calories). The type of fat and protein is also important. It appears unsaturated fat, like fish oil (omega 3 fatty acids) and monounsaturated fat, favorably affects testosterone more than saturated fat. Reducing animal protein in favor of vegetable protein can reduce resting testosterone levels and blunt the normal exercise-induced increase in testosterone.
Many factors influence testosterone levels and its biological activity. Some of these cannot be modified (aging, diurnal variation) while others are modifiable (obesity, diet, exercise). A hot topic addressed in this issue is testosterone boosters. This represents an exciting area for future research with great application for those wishing to enhance their testosterone levels naturally. Products marketed as testosterone boosters vary widely in quality and potency.
It's like the Wild West, so buyer beware. Be sure to check out the in depth review of the latest and greatest products aimed at altering testosterone levels in this issue.
REFERENCES CITED: Allan CA, McLachlan RI. Age-related changes in testosterone and the role of replacement therapy in older men. Clin Endocrinol (Oxf). 2004 Jun;60(6):653-70. B'langer, A., A. Locong, C. Noel, L. Cusan, A. Dupont, J. Pr'vost, S. Caron, and J. S'vigny. Influence of diet on plasma steroid and sex plasma binding globulin levels in adult men. J. Steroid Biochem. 32:829-833, 1989. Gromadzka-Ostrowska J, Przepiorka M, Romanowicz K. Influence of dietary fatty acids composition, level of dietary fat and feeding period on some parameters of androgen metabolism in male rats. Reprod Biol. 2002 Nov;2(3):277-93. Guezennec, P. Satabin, H. Legrand, and A.X. Bigard. Physical performance and metabolic changes induced by combined prolonged exercise and different energy intakes in humans. Eur. J. Appl. Physiol. 68:525-530, 1994. H'm'l'inen, E., H. Aldercreutz, P. Puska, and P. Pietinen. Diet and serum sex hormones in healthy men. J. Steroid Biochem. 20:459-464, 1984. Hill, P.B. and E.L. Wynder. Effect of a vegetarian diet and dexamethasone on plasma prolactin, testosterone and dehydroepiandrosterone in men and women. Cancer Letters. 7:273-282, 1979. Howie, B.J. and T.D. Shultz. Dietary and hormonal interrelationships among Seventh-Day Adventists and nonvegetarian men. Am. J. Clin. Nutr. 42:127-134, 1985. Key, T.J.A., L. Roe, M. Thorogood, J.W. Moore, G.M.G. Clark, and D.Y. Wang. Testosterone, sex hormone-binding globulin, calculated free testosterone, and oestradiol in male vegans and omnivores. Br. J. Nutr. 64:111-119, 1990. Kraemer WJ. Endocrine responses to resistance exercise. Med Sci Sports Exerc. 1988 Oct;20(5 Suppl):S152-7. Raben, A. B. Kiens, E.A. Ritchter, L.B. Rasmussen, B. Svenstrup, S. Micic, and P. Bennett. Serum sex hormones and endurance performance after a lacto-ovo vegetarian and a mixed diet. Med. Sci. Sports Exerc. 24:1290-1297, 1992. Ratamess NA, Kraemer WJ, Volek JS, Maresh CM, Vanheest JL, Sharman MJ, Rubin MR, French DN, Vescovi JD, Silvestre R, Hatfield DL, Fleck SJ, Deschenes MR. Androgen receptor content following heavy resistance exercise in men. J Steroid Biochem Mol Biol. 2005 Jan;93(1):35-42. Epub 2005 Jan 25. Reed, M.J., R.W. Cheng, M. Simmonds, W. Richmond, and V.H.T. James. Dietary Lipids: an additional regulator of plasma levels of sex hormone binding globulin. J. Clin. Endocrin. Metab. 64:1083-1085, 1987. Roemmich, J.N. and W.E. Sinning. Weight loss and wrestling training: effects on nutrition, growth, maturation, body composition, and strength. J. Appl. Physiol. 82:1751-9, 1977. Strauss, R.H., R.R. Lanese, and W.B. Malarkey. Weight loss in amateur wrestlers and its effect on serum testosterone levels. JAMA. 20;254:3337-8, 1985. Volek, J.S., M. Boetes, J.A. Bush, T. Incledon, and W.J. Kraemer. Testosterone and cortisol in relationship to dietary nutrients and heavy resistance exercise. J. Appl. Physiol. 82:49-54, 1997. Volek J.S., Gomez AL, Love DM, Avery NG, Sharman MJ, Kraemer WJ. Effects of a high-fat diet on postabsorptive and postprandial testosterone responses to a fat-rich meal. Metabolism. 2001 Nov;50(11):1351-5. Gauthaman K, et al., "Aphrodisiac properties of Tribulus Terrestris extract (Protodioscin) in normal and castrated rats," Life Sci (2002) 71.12 : 1385-1396. Brilla LR, Conte V. "Effects of zinc-magnesium formulation increases anabolic hormones and strength in athletes," Med Sci Sports Exer (1999) 31.5 : 483. Prasad AS, et al., "Zinc status and serum testosterone levels of healthy adults," Nutrition (1996) 12.5 : 344-348. Dorgan JF, et al., "Effects of dietary fat and fiber on plasma and urine androgens and estrogens in men: a controlled feeding study," Am J Clin Nutr (1996) 64.6 : 850-855. Liang T, Liao S. "Inhibition of steroid 5 alpha-reductase by specific aliphatic unsaturated fatty acids," J Biochem (1992) 285 ( Pt 2) : 557-562. Sebokova E, et al., "Alteration of the lipid composition of rat testicular plasma membranes by dietary (n-3) fatty acids changes the responsiveness of Leydig cells and testosterone synthesis," J Nutr (1990) 120.6 : 610-618. Bidzinska B, et al., "Effect of different chronic intermittent stressors and acetyl-l-carnitine on hypothalamic beta-endorphin and GnRH and on plasma testosterone levels in male rats," Neuroendocrinology (1993) 57.6 : 985-990.