How Quickly You Lose Muscle


“You can lose up to a kg of lean body mass in just a week when you’re fully immobilized”

11% decrease in type II muscle fibre size in just 10 days of no exercise

This is primarily due to a drop in glycogen and water levels within muscle tissue and NOT actually a loss of muscle tissue

“muscle glycogen can decrease by 20% after just a week without training

“Muscle glycogen levels and water stores will quickly refill once you start training again”

“Taking a couple of weeks off from the gym won’t cause any significant muscle loss, just a decrease in glycogen”

After 3+ weeks of no training is when you’ll typically start to experience actual muscle & strength loss”

Maintenance calories equation
bodyweight (in lbs) x 15 (example: 170 lbs x 15 = ~2550 calories to maintain weight

1g of protein per lb of body weight to gain muscle

“you only need around 1/3rd of your original training volume to maintain muscle mass”

“A high-intensity full body workout 1 – 2 times per week is likely enough to maintain muscle mass”



Glycogen and decreased muscle size:…………

3+ weeks muscle loss:……

Maintenance calories and protein intake:…

Stay active:……

Testosterone dose-response in healthy young men



Testosterone increases muscle mass and strength and regulates other physiological processes, but we do not know whether testosterone effects are dose dependent and whether dose requirements for maintaining various androgen-dependent processes are similar. To determine the effects of graded doses of testosterone on body composition, muscle size, strength, power, sexual and cognitive functions, prostate-specific antigen (PSA), plasma lipids, hemoglobin, and insulin-like growth factor I (IGF-I) levels, 61 eugonadal men, 18–35 yr, were randomized to one of five groups to receive monthly injections of a long-acting gonadotropin-releasing hormone (GnRH) agonist, to suppress endogenous testosterone secretion, and weekly injections of 25, 50, 125, 300, or 600 mg of testosterone enanthate for 20 wk.

Energy and protein intakes were standardized. The administration of the GnRH agonist plus graded doses of testosterone resulted in mean nadir testosterone concentrations of 253, 306, 542, 1,345, and 2,370 ng/dl at the 25-, 50-, 125-, 300-, and 600-mg doses, respectively. Fat-free mass increased dose dependently in men receiving 125, 300, or 600 mg of testosterone weekly (change +3.4, 5.2, and 7.9 kg, respectively). The changes in fat-free mass were highly dependent on testosterone dose (P = 0.0001) and correlated with log testosterone concentrations (r = 0.73, P = 0.0001). Changes in leg press strength, leg power, thigh and quadriceps muscle volumes, hemoglobin, and IGF-I were positively correlated with testosterone concentrations, whereas changes in fat mass and plasma high-density lipoprotein (HDL) cholesterol were negatively correlated. Sexual function, visual-spatial cognition and mood, and PSA levels did not change significantly at any dose.

We conclude that changes in circulating testosterone concentrations, induced by GnRH agonist and testosterone administration, are associated with testosterone dose- and concentration-dependent changes in fat-free mass, muscle size, strength and power, fat mass, hemoglobin, HDL cholesterol, and IGF-I levels, in conformity with a single linear dose-response relationship. However, different androgen-dependent processes have different testosterone dose-response relationships.

Testosterone regulates many physiological processes, including muscle protein metabolism, some aspects of sexual and cognitive functions, secondary sex characteristics, erythropoiesis, plasma lipids, and bone metabolism. However, testosterone dose dependency of various androgen-dependent processes is not well understood. Administration of replacement doses of testosterone to hypogonadal men and of supraphysiological doses to eugonadal men increases fat-free mass, muscle size, and strength.

Conversely, suppression of endogenous testosterone concentrations is associated with loss of fat-free mass and a decrease in fractional muscle protein synthesis. However, not known are whether testosterone effects on the muscle are dose dependent, or the nature of the testosterone dose-response relationships. Androgen receptors in most tissues are either saturated or downregulated at physiological testosterone concentrations; this leads to speculation that there might be two separate dose-response curves: one in hypogonadal range, with maximal response at low normal testosterone concentrations, and a second in supraphysiological range, representing a separate mechanism of action. However, testosterone dose-response relationships for a range of androgen-dependent functions in humans have not been studied.

Animal studies suggest that different androgen-dependent processes have different androgen dose-response relationships. Sexual function in male mammals is maintained at serum testosterone concentrations that are at the lower end of the male range. However, it is not known whether the low normal testosterone levels that normalize sexual function are sufficient to maintain muscle mass and strength, or whether the higher testosterone concentrations required to maintain muscle mass and strength might adversely affect plasma lipids, hemoglobin levels, and the prostate.

This information is important for optimizing testosterone replacement regimens for treatment of hypogonadal men. Also, for the proposed use of testosterone in sarcopenia associated with ageing and chronic illness, it is important to know whether significant gains in muscle mass and strength can be achieved at testosterone doses that do not adversely affect plasma high-density lipoprotein (HDL) and prostate-specific antigen (PSA) levels.

Therefore, the primary objective of this study was to determine the dose dependency of testosterone’s effects on fat-free mass and muscle performance. We hypothesized that changes in circulating testosterone concentrations would be associated with dose-dependent changes in fat-free mass, muscle strength, and power in conformity with a single linear dose-response relationship and that the dose requirements for maintaining other androgen-dependent processes would be different.

We treated young men with a long-acting gonadotropin-releasing hormone (GnRH) agonist to suppress endogenous testosterone secretion, and concomitantly also with one of five testosterone-dose regimens to create different levels of serum testosterone concentrations extending from subphysiological to the supraphysiological range. The lowest testosterone dose, 25 mg weekly, was selected because this dose had been shown to maintain sexual function in GnRH antagonist-treated men. The selection of the 600-mg weekly dose was based on the consideration that this was the highest dose that had been safely administered to men in controlled studies.




This was a double-blind, randomized study consisting of a 4-wk control period, a 20-wk treatment period, and a 16-wk recovery period. Each participant provided informed consent, approved by the institutional review boards of Drew University and Harbor-UCLA Research and Education Institute.


The participants were healthy men, 18–35 yr of age, with prior weight-lifting experience and normal testosterone levels. These men had not used any anabolic agents and had not participated in competitive sports events in the preceding year, and they were not planning to participate in competitive events in the following year.


Sixty-one eligible men were randomly assigned to one of five groups. All received monthly injections of a long-acting GnRH agonist to suppress endogenous testosterone production. In addition, group 1 received 25 mg of testosterone enanthate intramuscularly weekly;group 2, 50 mg testosterone enanthate; group 3, 125 mg testosterone enanthate; group 4, 300 mg testosterone enanthate; and group 5, 600 mg testosterone enanthate. Twelve men were assigned to group 1, 12 to group 2, 12 to group 3, 12 to group 4, and 13 togroup 5. Testosterone and GnRH agonist injections were administered by the General Clinical Research Center staff to assure compliance.

Nutritional intake.

Energy and protein intakes were standardized at 36 kcal · kg−1 · day−1 and 1.2 g · kg−1 · day−1, respectively. The standardized diet was initiated 2 wk before treatment was started; dietary instructions were reinforced every 4 wk. The nutritional intake was verified by analysis of 3-day food records and 24-h food recalls every 4 wk by use of the Minnesota Nutritional Software.

Exercise stimulus.

The participants were asked not to undertake strength training or moderate-to-heavy endurance exercise during the study. These instructions were reinforced every 4 wk.

Outcome measures.

Body composition and muscle performance were assessed at baseline and during week 20. Fat-free mass and fat mass were measured by underwater weighing and dual-energy X-ray absorptiometry (DEXA, Hologic 4500, Waltham, MA). Total thigh muscle and quadriceps muscle volumes were measured by MRI scanning.

For estimation of total body water, the men ingested 10 g of2H2O, and plasma samples were drawn at −15, 0, 120, 180, and 240 min. We measured2H abundance in plasma by nuclear magnetic resonance spectroscopy, with a correction factor of 0.985 for exchangeable hydrogen. We measured bilateral leg press strength by use of the one-repetition maximum (1-RM) method. A seated leg press exercise with pneumatic resistance (Keiser Sport, Fresno, CA) was used for this purpose. Subjects performed 5–10 min of leg cycling and stretching warm-up and received instruction and practice in lifting mechanics before performing progressive warm-up lifts leading to the 1-RM. Seat position and the ensuing knee and hip angles, as well as foot placement, were measured and recorded for use in subsequent testing.

To ensure reliability in this highly effort-dependent test, the 1-RM score was reassessed within 7 days, but not sooner than 2 days, after the first evaluation. If duplicate scores were within 5%, the higher of the two values was accepted as the strength score. If the two tests differed by >5%, additional studies were conducted, ≥2 days apart but within 7 days, until the two highest scores were within 5%. No subject required >2 days of strength assessment.

We also measured leg power, because power in the lower extremity is strongly related to the performance of functional activities in the elderly. The sarcopenia that accompanies ageing is due in large part to a loss of the fast-twitch type II fibers and the coincident decrease in explosive force. Muscular power is important in performing such daily activities as rising from a chair, climbing stairs, and walking with speed. Leg power was measured with a previously validated Nottingham leg extensor power rig. Subjects performed 10–15 trials of the right leg and hip extension, attempting to generate as much force as possible by accelerating the leg rig’s weighted flywheel from rest.

The power score (in watts) was taken as the highest value observed during these trials with evidence of a plateau. As with the strength tests, power measurements were preceded by a 5- to 10-min warm-up, stretching, and practice. The power tests were repeated within 7 days, but not sooner than 2 days, after the first tests to reduce the effect of familiarization. To minimize test-retest variability, the angle of knee flexion and the seat position were recorded and maintained constant across tests.

Sexual function was assessed by daily logs of sexual activity and desire that were maintained for 7 consecutive days at baseline and during treatment by use of a published instrument. Spatial cognition was assessed by a computerized checkerboard test and mood by Hamilton’s depression and Young’s mania scales.

Adverse experiences, blood counts and chemistries, PSA, plasma lipids, total and free testosterone, luteinizing hormone (LH), sex steroid-binding globulin (SHBG), and insulin-like growth factor I (IGF-I) levels were measured periodically during control and treatment periods. Serum total testosterone was measured by an immunoassay; free testosterone by equilibrium dialysis; LH, SHBG, and PSA by immunoradiometric assays; and IGF-I by acid-ethanol extraction and immunoassay. The sensitivities and intra- and interassay coefficients of variation for hormone assays were as follows: total testosterone (0.6 ng/dl), 8.2 and 13.2%; free testosterone (0.22 pg/ml), 4.2 and 12.3%; LH (0.05 U/l), 10.7 and 13.0%; SHBG (6.25 nmol/l), 4 and 6%; PSA (0.01 ng/ml), 5.0 and 6.4%; and IGF-I (80 ng/ml), 4 and 6%, respectively. These assays have been validated previously.

Statistical analyses.

All variables were examined for their distribution characteristics. Variables not meeting the assumption of a normal distribution were log-transformed and retested. An ANOVA was used to compare change from baseline in outcome measures among the five groups. All outcome measures were analyzed using a paired t-test to detect a non-zero change from baseline within each group. P < 0.05 was considered statistically significant.

To describe the relationship between testosterone concentrations (T) and change in fat-free mass (Y) during testosterone administration, we tested three models: a linear model (Y = a +bT); a logarithmic model, Y = a +b · X, where X = log (T), and a and b represent the intercept and slope, respectively; and a growth model, Y = a/(1 +b · e−k · X). The logarithmic model provided the best fit for the data and was used to model the effects of testosterone concentrations on the change in other outcome variables. The correlations between testosterone concentrations and change in outcome variables are derived from this model. We also modelled the linear dependence of the change in outcome variables on testosterone dose by use of linear regression.




Participant characteristics.

Of 61 men enrolled, 54 completed the study: 12 in group 1, 8 in group 2, 11 in group 3, 10 in group 4, and 13 in group 5. One man discontinued treatment because of acne; other subjects were unable to meet the demands of the protocol. The five groups did not significantly differ with respect to their baseline characteristics (Table1).



All evaluable subjects received 100% of their GnRH agonist injections, and only one man in the 125-mg group missed one testosterone injection.

Nutritional intake.

Daily energy intake and proportion of calories derived from protein, carbohydrate, and fat were not significantly different among the five groups at baseline. There was no significant change in daily caloric, protein, carbohydrate, or fat intake in any group during treatment (data not shown).

Hormone levels.

Serum total and free testosterone levels (Table2), measured during week 16, 1 wk after the previous injection, were linearly dependent on the testosterone dose (P = 0.0001). Serum total and free testosterone concentrations decreased from baseline in men receiving the 25- and 50-mg doses and increased at 300- and 600-mg doses. Serum LH levels were suppressed in all groups. Serum SHBG levels decreased dose dependently at the 300- and 600-mg doses but did not change in other groups. Serum IGF-I concentrations increased dose dependently at the 300- and 600-mg doses (correlation between log testosterone level and change in IGF-I = 0.55, P = 0.0001). IGFBP-3 levels did not change significantly in any group.


Body composition.

Fat-free mass, measured by underwater weighing, did not change significantly in men receiving the 25- or 50-mg testosterone dose, but it increased dose dependently at higher doses (Table3). The changes in fat-free mass were highly dependent on testosterone dose (P = 0.0001) and correlated with log total testosterone concentrations during treatment (r = 0.73, P = 0.0001, see Fig. 2).


Changes in fat-free mass, measured by DEXA scan, were qualitatively similar to those obtained from underwater weighing (Table3, Fig. 1). The measurements of fat-free mass by DEXA were highly correlated with values obtained from underwater weighing (r = 0.94, P < 0.0001)


Fig. 1.

Change in fat-free mass (A), fat mass (B), leg press strength (C), thigh muscle volume (D), quadriceps muscle volume (E), sexual function (F), insulin-like growth factor I (G), and prostate-specific antigen (H). Data are means ± SE. *Significant differences from all other groups (P < 0.05); ❖significant difference from 25-, 50-, and 125-mg doses (P < 0.05); +significant difference from 25- and 50-mg doses (P < 0.05); and ✞significant difference from 25-mg dose (P < 0.05).

To determine whether the apparent changes in fat-free mass by DEXA scan and underwater weighing represented water retention, we measured total body water and compared the ratios of total body water to fat-free mass before and after treatment in each group. The ratios of total body water to fat-free mass by underwater weighing did not significantly change with treatment in any treatment group (Table 3), indicating that the apparent increase in fat-free mass measured by underwater weighing did not represent water retention in excess of that associated with protein accretion.

Fat mass, measured by underwater weighing, increased significantly in men receiving the 25- and 50-mg doses but did not change in men receiving the higher doses of testosterone (Table 3, Fig. 1). There was an inverse correlation between change in fat mass by underwater weighing and log testosterone concentrations (r = −0.60, P = 0.0001, Fig.2).


Fig. 2.

Relationship between serum testosterone concentrations (T) during treatment (week 16) and change in fat-free mass (A), fat mass (B), leg press strength (C), thigh muscle volume (D), quadriceps muscle volume (E), sexual function (F), insulin-like growth factor I (G), and prostate-specific antigen (H). The correlation coefficient, r, was calculated using the logarithmic model, Y = a +b · X, where X = log (T), and a and represent the intercept and slope.

Muscle size.

The thigh muscle volume and quadriceps muscle volume did not significantly change in men receiving the 25- or 50-mg doses but increased dose dependently at higher doses of testosterone (Table4, Fig. 1). The changes in thigh muscle and quadriceps muscle volumes correlated with log testosterone levels during treatment (r = 0.66, P = 0.0001, and r = 0.55, P = 0.0001, respectively, Fig. 2).


Muscle performance.

The leg press strength did not change significantly in the 25- and 125-mg-dose groups but increased significantly in those receiving the 50-, 300-, and 600-mg doses (Table 5). The changes in leg press strength correlated with log testosterone levels during treatment (r = 0.48, P = 0.0005, Fig. 2) and changes in muscle volume (r = 0.54,P = 0.003) and fat-free mass (r = 0.74,P < 0.0001).


Leg power, measured by the Nottingham leg rig, did not change significantly in men receiving the 25-, 50-, and 125-mg doses of testosterone weekly, but it increased significantly in those receiving the 300- and 600-mg doses. The increase in leg power correlated with log testosterone concentrations (r = 0.39,P = 0.0105, Fig. 2) and changes in fat-free mass (r = 0.30, P = 0.0392) and muscle strength (r = 0.42, P = 0.0020).

Behavioural measures.

The scores for sexual activity and sexual desire measured by daily logs did not change significantly at any dose. Similarly, visual-spatial cognition (Table 6) and mood, as assessed by Hamilton’s depression and Young’s manic scales (data not shown), did not change significantly in any group.


Adverse experiences and safety measures.

Hemoglobin levels decreased significantly in men receiving the 50-mg dose but increased at the 600-mg dose; the changes in hemoglobin were positively correlated with testosterone concentrations (r = 0.66, P = 0.0001) (Table7). Changes in plasma HDL cholesterol, in contrast, were negatively dependent on testosterone dose (P = 0.0049) and correlated with testosterone concentrations (r = −0.40, P = 0.0054). Total cholesterol, plasma low-density lipoprotein cholesterol, and triglyceride levels did not change significantly at any dose. Serum PSA, creatinine, bilirubin, alanine aminotransferase, and alkaline phosphatase did not change significantly in any group, but aspartate aminotransferase decreased significantly in the 25-mg group. Two men in the 25-mg group, five in the 50-mg group, three in the 125-mg group, seven in the 300-mg group, and two in the 600-mg group developed acne. One man receiving the 50-mg dose reported decreased ability to achieve erections.




GnRH agonist administration suppressed endogenous LH and testosterone secretion; therefore, circulating testosterone concentrations during treatment were proportional to the administered dose of testosterone enanthate. This strategy of combined administration of GnRH agonist and graded doses of testosterone enanthate was effective in establishing different levels of serum testosterone concentrations among the five treatment groups. The different levels of circulating testosterone concentrations created by this regimen were associated with dose- and concentration-dependent changes in fat-free mass, fat mass, thigh and quadriceps muscle volume, muscle strength, leg power, hemoglobin, circulating IGF-I, and plasma HDL cholesterol. Serum PSA levels, sexual desire and activity, and spatial cognition did not change significantly at any dose. The changes in fat-free mass, muscle volume, leg press strength and power, hemoglobin, and IGF-I were positively correlated, whereas changes in plasma HDL cholesterol and fat mass were negatively correlated with testosterone dose and total and free testosterone concentrations during treatment.

The compliance with the treatment regimen was high. The participants received 100% of their scheduled GnRH agonist and 99% of testosterone injections. Serum LH levels were suppressed in all men, demonstrating the effectiveness of GnRH agonist treatment. The treatment regimen was well tolerated. There were no significant changes in PSA or liver enzymes at any dose. However, long-term effects of androgen administration on the prostate, cardiovascular risk, and behaviour are unknown.

Serum testosterone levels were measured 7 days after the previous injection; they reflect the lowest testosterone levels after an injection. Testosterone concentrations were higher at other time points. Weekly injections of testosterone enanthate are associated with fluctuations in testosterone levels. Although nadir testosterone concentrations were highly correlated with testosterone enanthate dose, it is possible that sustained testosterone delivery by a patch or gel might reveal different dose-response relationships, particularly with respect to hemoglobin and HDL cholesterol.

There were no significant changes in overall sexual activity or sexual desire in any group, including those receiving the 25-mg dose. Testosterone replacement of hypogonadal men improves the frequency of sexual acts and fantasies, sexual desire, and response to visual erotic stimuli. Our data demonstrate that serum testosterone concentration at the lower end of the male range can maintain some aspects of sexual function. Testosterone has been shown to regulate nitric oxide synthase activity in the cavernosal smooth muscle, and it is possible that optimum penile rigidity might require higher testosterone levels than those produced by the 25-mg dose.

This study demonstrates that an increase in circulating testosterone concentrations results in dose-dependent increases in fat-free mass, muscle size, strength, and power. The relationships between circulating testosterone concentrations and changes in fat-free mass and muscle size conform to a single log-linear dose-response curve. Our data do not support the notion of two separate dose-response curves reflecting two independent mechanisms of testosterone action on the muscle. Forbes et al. predicted 25 years ago that the muscle mass accretion during androgen administration is related to the cumulative androgen dose, the product of daily dose and treatment duration. Our data are consistent with Forbes’s hypothesis of a linear relationship between testosterone dose and lean mass accretion; however, we do not know whether increasing the treatment duration would lead to further gains in muscle mass.

In addition, we do not know whether responsiveness to testosterone is attenuated in older men. Testosterone dose-response relationships might be modulated by other muscle growth regulators, such as nutritional status, exercise and activity level, glucocorticoids, thyroid hormones, and endogenous growth hormone secretory status.

Serum PSA levels decrease after androgen withdrawal, and testosterone replacement of hypogonadal men increases PSA levels into the normal range. We did not find significant changes in PSA at any dose, indicating that the lowest dose of testosterone maintained PSA levels. We did not measure prostate volume in this study; therefore, we do not know whether prostate volume exhibits the same relationship with testosterone dose as PSA levels.

Hemoglobin levels changed significantly in relation to testosterone dose and concentration. Testosterone regulates erythropoiesis through its effects on erythropoietin and stem cell proliferation (1. Although modest increments in hemoglobin might be beneficial in androgen-deficient men with chronic illness who are anemic, marked increases in hemoglobin levels could increase the risk of cerebrovascular events and hypertension.

Although men, on average, perform better on tests of spatial cognition than women, testosterone replacement has not been consistently shown to improve spatial cognition in hypogonadal men. We did not find changes in spatial cognition at any dose. The effect size of gender differences in spatial cognition is small; it is possible that our study did not have sufficient power to detect small differences. We cannot exclude the possibility that gender differences in spatial cognition might be due to organizational effects of testosterone and might not respond to changes in testosterone levels in adult men.

Although the mean change in fat-free mass and muscle size correlated with testosterone dose and concentration, there was considerable heterogeneity in response to testosterone administration within each group. These individual differences in response to androgen administration might reflect differences in activity level, testosterone metabolism, nutrition, or polymorphisms in androgen receptor, myostatin, 5-α-reductase, or other muscle growth regulators.

Our data demonstrate that different androgen-dependent processes have different testosterone dose-response relationships. Some aspects of sexual function and spatial cognition, and PSA levels, were maintained by relatively low doses of testosterone in GnRH agonist-treated men and did not increase further with administration of higher doses of testosterone. In contrast, graded doses of testosterone were associated with dose and testosterone concentration-dependent changes in fat-free mass, fat mass, muscle volume, leg press strength and power, hemoglobin, IGF-I, and plasma HDL cholesterol. The precise mechanisms for the tissue- and function-specific differences in testosterone dose dependence are not well understood. Although only a single androgen receptor protein is expressed in all androgen-responsive tissues, tissue specificity of androgen action might be mediated through combinatorial recruitment of tissue-specific coactivators and corepressors.

Testosterone doses associated with significant gains in fat-free mass, muscle size, and strength were associated with significant reductions in plasma HDL concentrations. Further studies are needed to determine whether clinically significant anabolic effects of testosterone can be achieved without adversely affecting cardiovascular risk. Selective androgen receptor modulators that preferentially augment muscle mass and strength, but only minimally affect prostate and cardiovascular risk factors, are desirable.

This study was supported primarily by National Institutes of Health (NIH) Grant 1RO1-AG-14369; additional support was provided by Grants 1RO1-DK-49296, 1RO1-DK-59297–01, Federal Drug Administration Grant ODP 1397, a General Clinical Research Center Grant MO-00425, NIH-National Center for Research Resources-00954, RCMI Grants P20-RR-11145–01 (RCMI Clinical Research Initiative) and G12-RR-03026. BioTechnology General (Iselin, NJ) provided testosterone enanthate, and R. P. Debio (Martigny, Switzerland) provided the GnRH agonist (Decapeptyl)





1. Alexander GM , Swerdloff RS , Wang C , Davidson T , McDonald V , Steiner B , Hines M. .Androgen-behavior correlations in hypogonadal men and eugonadal men. II. Cognitive abilities..Horm Behav 33: 85-94, 1998.
Crossref PubMed ISI Google Scholar

2. Antonio J , Wilson JD , George FW. .Effects of castration and androgen treatment on androgen-receptor levels in rat skeletal muscles..J Appl Physiol 87: 2016-2019, 1999.
Abstract ISI Google Scholar

3. Bagatell CJ , Heiman JR , Rivier JE , Bremner WJ. .Effects of endogenous testosterone and estradiol on sexual behavior in normal young men..J Clin Endocrinol Metab 78: 711-716, 1994.
PubMed ISI Google Scholar

4. Bassey EJ , Fiatarone MA , O’Neill EF , Kelly M , Evans WJ , Lipsitz LA. .Leg extensor power and functional performance in very old men and women..Clin Sci (Colch) 82: 321-327, 1992.
Crossref Google Scholar

5. Bassey EJ , Short AH. .A new method for measuring power output in a single leg extension: feasibility, reliability and validity..Eur J Appl Physiol 60: 385-390, 1990.
Crossref ISI Google Scholar

6. Bhasin S. .The dose-dependent effects of testosterone on sexual function and on muscle mass and function..Mayo Clin Proc 75, Suppl: S70-S75, 2000.
PubMed Google Scholar

7. Bhasin S , Bremner WJ. .Clinical review 85: emerging issues in androgen replacement therapy..J Clin Endocrinol Metab 82: 3-8, 1997.
PubMed ISI Google Scholar

8. Bhasin S , Fielder TJ , Peacock N , Sod-Moriah UA , Swerdloff RS. .Dissociating antifertility effects of GnRH-antagonist from its adverse effects on mating behavior in male rats..Am J Physiol Endocrinol Metab 254: E84-E91, 1988.
Link ISI Google Scholar

9. Bhasin S , Storer TW , Berman N , Callegari C , Clevenger B , Phillips J , Bunnell TJ , Tricker R , Shirazi A , Casaburi R. .The effects of supraphysiologic doses of testosterone on muscle size and strength in normal men..N Engl J Med335: 1-6, 1996.
Crossref PubMed ISI Google Scholar

10. Bhasin S , Storer TW , Berman N , Yarasheski KE , Cleveneger B , Casaburi RA. .A replacement dose of testosterone increases fat-free mass and muscle size in hypogonadal men..J Clin Endocrinol Metab 82: 407-413, 1997.
PubMed ISI Google Scholar

11. Bhasin S , Storer TW , Javanbakht M , Berman N , Yarasheski KE , Phillips J , Dike M , Sinha-Hikim I , Shen R , Hays RD , Beall G. .Testosterone replacement and resistance exercise in HIV-infected men with weight loss and low testosterone levels..JAMA 283: 763-770, 2000.
Crossref PubMed ISI Google Scholar

12. Brodsky IG , Balagopal P , Nair KS. .Effects of testosterone replacement on muscle mass and muscle protein synthesis in hypogonadal men—a clinical research center study..J Clin Endocrinol Metab 81: 3469-3475, 1996.
PubMed ISI Google Scholar

13. Buena F , Swerdloff RS , Steiner BS , Lutchmansingh P , Peterson MA , Pandian MR , Galmarini M , Bhasin S. .Sexual function does not change when serum testosterone levels are pharmacologically varied within the normal male range..Fertil Steril 59: 1118-1123, 1993.
Crossref PubMed ISI Google Scholar

14. Byron JW. .Effect of steroids on the cycling of haemopoietic stem cells..Nature 228: 1204-1206, 1970.
Crossref PubMed ISI Google Scholar

15. Carani C , Granata AR , Bancroft J , Marrama P. .The effects of testosterone replacement on nocturnal penile tumescence and rigidity and erectile response to visual erotic stimuli in hypogonadal men..Psychoneuroendocrinology 20: 743-753, 1995.
Crossref PubMed ISI Google Scholar

16 .Cooper CS , Perry PJ , Sparks AE , MacIndoe JH , Yates WR , Williams RD. .Effect of exogenous testosterone on prostate volume, serum and semen prostate specific antigen levels in healthy young men..J Urol 159: 441-443, 1998.
Crossref PubMed ISI Google Scholar

17. Cunningham GR , Hirshkowitz M , Korenman SG , Karacan I. .Testosterone replacement therapy and sleep-related erections in hypogonadal men..J Clin Endocrinol Metab 70: 792-797, 1990.
Crossref PubMed ISI Google Scholar

18. Dahlberg E , Snochowski M , Gustafsson J-A. .Regulation of androgen and glucocorticoid receptors in rat and mouse skeletal muscle cytosol..Endocrinology 108: 1431-1440, 1981.
Crossref PubMed ISI Google Scholar

19. Dobs AS , Meikle AW , Arver S , Sanders SW , Caramelli KE , Mazer NA. .Pharmacokinetics, efficacy, and safety of a permeation-enhanced testosterone transdermal system compared with bi-weekly injections of testosterone enanthate for the treatment of hypogonadal men..J Clin Endocrinol Metab 84: 3469-3478, 1999.
PubMed ISI Google Scholar

20. Faries D , Herrera J , Rayamajhi J , DeBrota D , Demitrack M , Potter WZ. .The responsiveness of the Hamilton Depression Rating Scale..J Psychiatr Res 34: 3-10, 2000.
Crossref PubMed ISI Google Scholar

21. Fielder TJ , Peacock NR , McGivern RF , Swerdloff RS , Bhasin S. .Testosterone dose-dependency of sexual and nonsexual behaviors in the gonadotropin-releasing hormone antagonist-treated male rat..J Androl 10: 167-173, 1989.
Crossref PubMed Google Scholar

22. Forbes GB. .The effect of anabolic steroids on lean body mass: the dose response curve..Metabolism 34: 571-573, 1985.
Crossref PubMed ISI Google Scholar

23. Forbes GB , Porta CR , Herr BE , Griggs RC. .Sequence of changes in body composition induced by testosterone and reversal of changes after drug is stopped..JAMA 267: 397-399, 1992.
Crossref PubMed ISI Google Scholar

24. Fristad MA , Weller RA , Weller EB. .The Mania Rating Scale (MRS): further reliability and validity studies with children..Ann Clin Psychiatry 7: 127-132, 1995.
Crossref PubMed Google Scholar

25. Gillum RF , Sempos CT. .Hemoglobin, hematocrit, and stroke incidence and mortality in women and men..Stroke 27: 1910-1914, 1996.
PubMed ISI Google Scholar

26. Griggs RC , Kingston W , Jozefowicz RF , Herr BE , Forbes G , Halliday D. .Effect of testosterone on muscle mass and muscle protein synthesis..J Appl Physiol 66: 498-503, 1989.
Link ISI Google Scholar

27. Grinspoon S , Corcoran C , Askari H , Schoenfeld D , Wolf L , Burrows B , Walsh M , Hayden D , Parlman K , Anderson E , Basgoz N , Klibanski A. .Effects of androgen administration in men with the AIDS wasting syndrome: a randomized, double-blind, placebo-controlled trial..Ann Intern Med 129: 18-26, 1998.
Crossref PubMed ISI Google Scholar

28. Hornum M , Cooper DM , Brasel JA , Bueno A , Sietsema KE. .Exercise-induced changes in circulating growth factors with cyclic variation in plasma estradiol in women..J Appl Physiol 82: 1946-1951, 1997.
Link ISI Google Scholar

29. Janowsky JS , Oviatt SK , Orwoll ES. .Testosterone influences spatial cognition in older men..Behav Neurosci 108: 325-332, 1994.
Crossref PubMed ISI Google Scholar

30. Katznelson L , Finkelstein JS , Schoenfeld DA , Rosenthal DI , Anderson EJ , Klibanski A. .Increase in bone density and lean body mass during testosterone administration in men with acquired hypogonadism..J Clin Endocrinol Metab 81: 4358-4365, 1996.
PubMed ISI Google Scholar

31. Kwan M , Greenleaf WJ , Mann J , Crapo L , Davidson JM. .The nature of androgen action on male sexuality: a combined laboratory- self-report study on hypogonadal men..J Clin Endocrinol Metab 57: 557-562, 1983.
Crossref PubMed ISI Google Scholar

32. Lugg JA , Rajfer J , Gonzalez-Cadavid NF. .Dihydrotestosterone is the active androgen in the maintenance of nitric oxide-mediated penile erection in the rat..Endocrinology 136: 1495-1501, 1995.
Crossref PubMed ISI Google Scholar

33. Mauras N , Hayes V , Welch S , Veldhuis J , Urban R. .Testosterone deficiency in young men: marked alterations in whole body protein kinetics, strength, and adiposity..J Clin Endocrinol Metab83: 1886-1892, 1998.
PubMed ISI Google Scholar

34. Meikle AW , Arver S , Dobs AS , Adolfsson J , Sanders SW , Middleton RG , Stephenson RA , Hoover DR , Rajaram L , Mazer NA. .Prostate size in hypogonadal men treated with a nonscrotal permeation-enhanced testosterone transdermal system..Urology 49: 191-196, 1997.
Crossref PubMed ISI Google Scholar

35. Naets JP , Wittek M. .Mechanism of action of androgens on erythropoiesis..Am J Physiol210: 315-320, 1966.
Abstract ISI Google Scholar

36. Negro-Vilar A. .Selective androgen receptor modulators (SARMs): a novel approach to androgen therapy for the new millennium..J Clin Endocrinol Metab 84: 3459-34362, 1999.
Crossref PubMed ISI Google Scholar

37. Pavlou SN , Brewer K , Farley MG , Lindner J , Bastias MC , Rogers BJ , Swift LL , Rivier JE , Vale WW , Conn PM. .Combined administration of a gonadotropin-releasing hormone antagonist and testosterone in men induces reversible azoospermia without loss of libido..J Clin Endocrinol Metab 73: 1360-1369, 1991.
Crossref PubMed ISI Google Scholar

38. Pope HG , Jacobs A. .Evidence for sex-specific residual effect of cannabis on visuo-spatial memory..Psychother Psychosom 66: 179-184, 1997.
Crossref PubMed ISI Google Scholar

39. Rance NE , Max SR. .Modulation of the cytosolic androgen receptor in striated muscle by sex-steroids..Endocrinology 115: 862-866, 1984.
Crossref PubMed ISI Google Scholar

40. Rencricca NJ , Solomon J , Fimian WJ , Howard D , Rizzoli V , Stohlman F .The effect of testosterone on erythropoiesis..Scand J Haematol 6: 431-436, 1969.
PubMed Google Scholar

41. Salmimies P , Kockott G , Pirke KM , Vogt HJ , Schill WB. .Effects of testosterone replacement on sexual behavior in hypogonadal men..Arch Sex Behav 11: 345-353, 1982.
Crossref PubMed ISI Google Scholar

42. Siebers RW , Carter JM , Maling TJ. .Increase in haematocrit in borderline hypertensive men..Clin Exp Pharmacol Physiol 21: 401-403, 1994.
Crossref PubMed ISI Google Scholar

43. Sinha-Hikim I , Arver S , Beall G , Shen R , Guerrero M , Sattler F , Shikuma C , Nelson JC , Landgren BM , Mazer NA , Bhasin S. .The use of a sensitive, equilibrium dialysis method for the measurement of free testosterone levels in healthy, cycling women, and in HIV-infected women..J Clin Endocrinol Metab 83: 1312-1318, 1998.
PubMed ISI Google Scholar

44. Snyder PJ , Lawrence DA. .Treatment of male hypogonadism with testosterone enanthate..J Clin Endocrinol Metab 51: 1335-1339, 1980.
Crossref PubMed ISI Google Scholar

45. Snyder PJ , Peachey H , Berlin JA , Hannoush P , Haddad G , Dlewati A , Santanna J , Loh L , Lenrow DA , Holmes JH , Kapoor SC , Atkinson JE , Strom BLE .Effects of testosterone replacement in hypogonadal men..J Clin Endocrinol Metab85: 2670-2677, 2000.
PubMed ISI Google Scholar

46. Snyder PJ , Peachey H , Hannoush P , Berlin JA , Loh L , Lenrow DA , Holmes JH , Dlewati A , Santanna J , Rosen CJ , Strom BL. .Effect of testosterone treatment on body composition and muscle strength in men over 65 years of age..J Clin Endocrinol Metab 84: 2647-2653, 1999.
PubMed ISI Google Scholar

47. Tenover JS. .Androgen replacement therapy to reverse and/or prevent age-associated sarcopenia in men..Bailliere’s Clin Endocrinol Metab 12: 419-425, 1998.
Crossref PubMed ISI Google Scholar

48. Van Goozen SH , Cohen-Kettenis PT , Gooren LJ , Frijda NH , Van de Poll NE. .Activating effects of androgens on cognitive performance: causal evidence in a group of female-to-male transsexuals..Neuropsychologia 32: 1153-1157, 1994.
Crossref PubMed ISI Google Scholar

49. Wang C , Swedloff RS , Iranmanesh A , Dobs A , Snyder PJ , Cunningham G , Matsumoto AM , Weber T , Berman N. .Transdermal testosterone gel improves sexual function, mood, muscle strength, and body composition parameters in hypogonadal men. Testosterone Gel Study Group..J Clin Endocrinol Metab 85: 2839-2853, 2000.
PubMed ISI Google Scholar

50. Wilson JD. .Androgen abuse by athletes..Endocr Rev 9: 181-199, 1988.







Authors – Shalender Bhasin,  Linda Woodhouse, Richard Casaburi, Atam B. Singh, Dimple Bhasin, Nancy Berman, Xianghong Chen, Kevin E. Yarasheski, Lynne Magliano, Connie Dzekov, Jeanne Dzekov, Rachelle Bross, Jeffrey Phillips, Indrani Sinha-Hikim. Ruoquing Shen and Thomas W.

Lifting 3 Days a Week Is Best. More Gains. Less Gym!

mens health 4 - Copy

A Better Way to Lift Weights

One of the most fundamental decisions every lifter needs to make is how often he or she needs to train each week. A related question is how often each muscle or body part needs to be trained each week.

Train too often and you can’t recover. Don’t train enough and you regress to (or below) baseline between workouts. Obviously, this is an important programming factor! If you’re like most lifters, your ideal workout frequency is three times per week.

This recommendation contrasts sharply with a few of the more popular training styles practised today:

  • Squat Every Day: I’ve seen some compelling arguments made for the so-called “Bulgarian” approach by coaches I like and respect, but for reasons I’ll outline below, the high-frequency lifestyle is less than optimal for most.
  • Bro-Splits: This is where you have a leg day, a back day, an arm day, and so on. Everything gets hit roughly once a week. If you’re so damn big and strong that you need six days to recover from training a body part, then this is a great training structure. But assess yourself honestly – does your chest workout mess you up so badly that you need almost a week to recover? Probably not.
  • Push-Pull: This is the “next best” of these three examples, but two upper and two lower days per week probably isn’t enough frequency, unless you can bench over 350 and squat over 500. If you haven’t quite arrived at these numbers yet, you’ll be better off training each body part a bit more often.

Success Leaves Clues

If you haven’t done much research on the bodybuilding, weightlifting, and powerlifting stars of the 50’s, 60’s, and 70’s, you might be more impressed than you expect.

Despite the relatively primitive state of drugs, nutritional science, and recovery modalities back then, there were plenty of strength and physique athletes who could give today’s stars a run for their money, guys like Franco Columbo, Anatoly Pisarenko, Bill Kazmaier, and Doug Young, just to name a handful.

That’s not to say all successful strength and physique athletes trained three days a week back in the day, but a lot of them did. And in fact, one of the most well-established and successful training routines of all time is the legendary “5×5” program by Bill Starr, which – you guessed it – used a three-day training structure.

This program (and variations of it) are the bread and butter of strength coach and T Nation contributor Mark Rippetoe, who specializes in beefing up young guys so fast that they’re often accused of juicing.

Who’s Best Suited For Training 3 Days A Week?

Probably you. Three training days a week tends to work best for guys between 185 and 225 (84 and 103kg) pounds with lifts in the following neighborhood:

  • Squat: 300-350 pounds (136 – 160kg)
  • Bench: 225-275 pounds (103 – 125kg)
  • Deadlift: 365-405 pounds (165 – 185kg)

If you’re significantly smaller and/or weaker than this, consider whole body workouts about four times a week or roughly every other day. If you’re stronger, go with the push/pull system. If you’re freakishly big and strong, go with the bro-split, bro.

There’s also a lifestyle consideration that impacts this decision. If you work a lot, especially in a physical job, or have high levels of stress or outside commitments, limiting your workouts to three a week will pay off in spades. Training is only beneficial if you can recover from it, and your workouts are only one form of stress you experience in the course of a day.

It should be noted that back in the 50’s, 60’s, and 70’s, most occupations involved more physical labor than they do today. This is likely one big reason (along with fewer pharmaceuticals) why the three-day training schedule worked so well. So if you work construction, or are just on your feet all day at your job, three days a week will be a game changer.

Finally, remember that the law of diminishing returns applies to training frequency in an unmistakable way: Is training twice a week better than once a week? You bet. A lot better. Is three times a week better than two? Nearly all training experts would say yes. What about four times a week? Here’s where things begin to get “iffy.”

For some people yes, others no. But in either event, even if four is better than three, it’s likely only marginally better. So even if you doubt the premise that three sessions a week is better than four, you can’t as easily dismiss the efficiency of getting perhaps 90% of the payoff with 75% of the work.

With all of that in mind, a very practical litmus test to fine tune your training frequency is to look at your progress in the gym. If you’re working hard and getting results, you’re probably dialed in. On the other hand, if you’re busting tail and not making progress, this means you’re not recovering and should consider reducing your training frequency.

The Advantages Of Training 3 Days A Week

1 – Greater Frequency

All else being equal, the more you can disperse your training volume over a greater number of sessions, the better you’re likely to do.

If we compare three days a week with the push/pull system for instance, you’ll notice something interesting. Let’s say you typically do 4 working sets for chest, and of course, on the push/pull system, that means 8 sets a week per chest exercise.

When you shift to a whole-body, three days-a-week structure, you’re now using 12 sets a week, since you’ll now be training chest three days instead of two. That’s a 50% increase. Seems significant, right? And what’s more important, if you’re benching in the 225-275 range, is you’re probably going to recover in two days, not three to four.

If you don’t repeat the training stimulus as soon as you’re recovered, you’ll lose a bit of ground. Week by week, month by month, this adds up to a lot of lost ground.

2 – Better Recovery

When you lift three days a week, by definition, you’re recovering four days a week. Juxtapose this with the earlier point about training more frequently and you begin to see the magic. You actually train each body part more often, while simultaneously allowing for more recovery. That’s tough to beat.

By “recovery” I mean passive and (possibly even better) active recovery. You could simply rest on your four off days, or do complementary activities such as cardio, foam rolling, mobility work, and so on. When you train on a Monday/Wednesday/Friday schedule, you can schedule these restorative activities on Tuesday/Thursday/Saturday, and then take Sunday totally off if you like.

3 – Better Compliance

In a recent interview, certified freak of nature and self-proclaimed “World’s Strongest Bodybuilder” Stan Efferding stated that consistency is at the top of the list when it comes to training considerations.

He meant that no matter how “optimal” a given system or approach is, if you can’t or won’t do it consistently, it’s not going to pay off. Training three days a week allows time for a life outside of lifting – weekends off with the family, time for other hobbies, and enough energy to attend to life’s responsibilities without becoming overwhelmed. Consider this if life stress is affecting your workouts.


How It Looks

When you train thrice a week, you’ll be doing whole-body workouts, meaning, you’ll train both upper and lower body in each session. These workouts can (and usually should) be a tad longer than what you’d use if you were training more frequently. Here’s what a sample training week might look like:


  • Split Squat
  • Flat Dumbbell Bench
  • Romanian Deadlift
  • Close-Grip Pulldown
  • Standing Dumbbell Curl
  • Lying Triceps Extension


  • Pull-Up
  • Back Extension
  • Bench Press
  • Hack Squat
  • Triceps Pushdown
  • Low Cable Curl


  • Deadlift
  • T-Bar Row
  • Front Squat
  • Incline Dumbbell Press
  • EZ-Bar Curl
  • Standing Calf Raise

Notice a few things about this hypothetical example:

  • The first four movements in each session represent the four primary patterns for strength and hypertrophy development (squat, push, hinge, and pull). The last two exercises in each workout are “optional” movements – things you like to do, or should be doing, that don’t fit neatly into the four patterns.
  • These could be anything from direct arm, calf, or ab work, to weighted carries, power cleans, box jumps, or whatever else might fit your needs and circumstances. There’s lots of flexibility here, so take advantage.
  • The overriding point is this: If you train the four “big” patterns three times a week each, you’ll be stimulating a lot of muscular territory, with the fewest possible number of exercises, with minimal redundancy. In other words, maximum return for your training dollar.
  • In each “neighboring” workout, the exercises selected for each primary pattern are as dissimilar as possible. If you do a vertical pull and a horizontal push on Monday, you’ll do a horizontal pull and a vertical push on Wednesday. Since fatigue is specific, varying exercises as much as possible (within the confines of the given template) will allow you to recover faster, and you’ll also be less prone to pattern-overload (overuse) injuries.
  • In a Monday/Wednesday/Friday setup, you’ll have more recovery time after the Friday session than you’ll have after the Monday and Wednesday workouts. For this reason, place the most damaging exercises – the ones that will require the most recovery – on Friday.
  • For me, this means deadlifts, but for you it might be something else. I also tend to be more willing to go hard on the optionals on Friday, knowing I’ve got more days to heal up. So you might use that day for weighted carries or something similarly masochistic.
  • The Friday session can also be shifted to Saturday with minimal (if any) negative effect on the overall program. So if you’re more sore than you anticipated on Friday, or if an unexpected interruption crops up, you’ve got enough flexibility to make adjustments with no repercussions.

Adding “Supportive” Activities To This Template

Lifting is a bit like cooking in that it results in a great meal, but also a messy kitchen. For many lifters, your off days are best spent working on cleaning the kitchen before it’s time to cook again.

In my own case, I love to bench and tend to be a bit kyphotic, so I spend time doing mobility drills for my upper back, chest, and shoulders on my non-lifting days, and I also do a fair bit of walking just to move some blood around and burn a few calories.

If fat loss is a big part of your goal, those off days are the best time to do formal cardio to accelerate energy expenditure and fat loss. If you’re a recreational athlete, use your non-lifting days to practice your sport of choice. Lots of possibilities here. Explore them all.

Now Make It Your Own

If you’re working hard without satisfactory results while training four or more days a week, or if you have a physically demanding occupation, or just have a lot of responsibilities and stresses in life, give this approach an honest run.

Remember, there’s a lot of room for customization with this template, regardless of whether you’re a weightlifter, bodybuilder, powerlifter, strongman athlete, or just a serious recreational lifter. Just apply this template and its foundational principles to your own situation.

Charles Staley is an accomplished strength coach who specializes in helping older athletes reclaim their physicality and vitality. At age 56, Charles is leaner than ever, injury free, and in his lifetime best shape. His PRs include a 400-pound squat, 510-pound deadlift, and a 17 chin-up max. 

Original article by Charles Staley@t-nation

Listening to music while exercising activates specific brain regions — and could help stave off fatigue

brain scan

New neuroimaging research sheds light on how music can help people shield themselves from feelings of fatigue while exercising. The study, published in the International Journal of Psychophysiology, found that listening to music while exercising was linked to increased activity in a particular brain region.

“As a researcher I have always been interested in unravelling psychophysiological mechanisms. The effects of music on exercise have been systematically investigated for more than 100 years, and we are still not completely sure how music enhances exercise performance, assuages fatigue, and elicits positive affective responses,” said study author Marcelo Bigliassi of Brunel University London.

“I have spent the past decade trying to answer this research question and, finally, after a series of fNIRS (functional near-infrared spectroscopy)EEG (electroencephalography), and fMRI (functional magnetic resonance imaging) experiments, we can now understand how music is processed in the brain during exercise.”

In the study of 19 healthy adults, participants laid down in an MRI scanner and exercised using a hand strengthener grip ring. The participants executed 30 exercise sets, which each lasted for 10 minutes. During some of these sets, the participants listened to Creedence Clearwater Revival’s I Heard It Through The Grapevine.

Bigliassi and his colleagues found that the presence of music was associated with greater excitement during exercise along with an increase in thoughts that were unrelated to the task. They also observed changes in a particular region of the brain.

“Music is a very powerful auditory stimulus and can be used to assuage negative bodily sensations that usually arise during exercise-related situations. This psychophysical response is triggered by an attentional mechanism that will ultimately result in a more efficacious control of the musculature,” Bigliassi told PsyPost.

“What we have identified in this study was that the left inferior frontal gyrus activates (see the Figure below) when individuals exercise in the presence of music. This region of the brain appears to be a hub of sensory integration, processing information from external and internal sources (e.g., music and limb discomfort, respectively).”

“Increased activation of this region was negatively correlated with exertional responses, meaning that the more active this region the less fatigue participants experienced,” Bigliassi said. “It is important to emphasise that the practical implications of this study might be very similar to other applied studies in the field of sport and exercise. However, unravelling these mechanisms can actually open a new avenue for scientific investigation into the effects of sensory modulation on attentional responses and subsequent fatigue-related sensations.”

“For example, it is possible that other forms of stimulation (e.g., electrical) could lead to a series of domino reactions that might facilitate the execution of movements performed at moderate-to-high intensities and lessen fatigue. This could be used during the most critical periods of the exercise regimen, when high-risk individuals are more likely to disengage from physical activity programmes (e.g., individuals with obesity, diabetes, and etc.).”

Another of Bigliassi’s studies used portable EEG technology to find that listening to music while walking reduced focus but increased energy levels and enjoyment. The effects were associated with an increase in beta waves in the frontal and frontal-central regions of the cortex.

But Bigliassi does not want to overstate the positive effects of music.

“I have some practical concerns about the exaggerated use of music and other forms of stimulation during exercise that are relevant to share. This is because, as humans, we are constantly trying to escape from reality and, also, escape from all forms of physical discomfort/pain,” he explained.

“We have learnt so much about the psychophysical, psychological, and psychophysiological effects of music in the past two decades that people are almost developing a peculiar form of stimulus dependence. If we continue to promote the unnecessary use of auditory and visual stimulation, the next generation might be no longer able to tolerate fatigue-related symptoms and exercise in the absence of music.”

“My view is that music and audiovisual stimuli can and should be used and promoted, but with due care,” Bigliassi said. “We should, perhaps, learn more about the joys of physical activity and develop methods/techniques to cope with the detrimental effects of fatigue (i.e., learn how to listen to our bodies and respect our biomechanical and physiological limitations).”


The study, “Cerebral effects of music during isometric exercise: An fMRI study“, Marcelo Bigliassi, Costas I. Karageorghis, Daniel T. Bishop, Alexander V. Nowicky, and Michael J. Wright.



Original article by @psypost



Overview and Summary


Alpha GPC is a naturally occurring choline intermediary that is formed when the body breaks down cell membranes for choline. As a supplement Alpha GPC is a highly bio available form of choline that crosses the blood brain barrier and raises brain levels of choline. Inside the brain choline supports cell membrane and neurotransmitter synthesis. Of all the supplemental forms of choline, GPC is probably the most cholinergic per gram, as it’s 40% choline by weight and appears to be well absorbed.

All of the available research is discussed below, a summary of the research finds that GPC is able to:

  • Support cell membrane synthesis and cell membrane fluidity (10)
  • Reduce age related declines in muscarinic (M1) receptors (2)(10)
  • Support acetylcholine synthesis (7)(13)(15)(16)
  • Increase pre-synaptic choline transporters (11)(12)
  • Prevent anti-cholinergic induced cognitive deficits (7)(13)(15)(16)
  • Raise memory/recall above baseline in a small pilot study (15)
  • Enhance growth hormone output (4)(8)
  • Enhance peak muscular force during exercise (4)
  • Improve cognitive function in elderly dementia patients (5)(9)(14)
  • Remain free of side effects at therapeutic doses (2.4% total reported in dementia patients) (17)

Other Names

A-GPCAlpha-glycerophosphocholine, choline alphoscerate, GPC.

Important Information


600mg pre-exercise was shown to enhance power output, endurance and growth hormone release (4)

1200mg daily (3 doses 400mg) has been administered in clinical trials to relieve cognitive decline in patients with dementia (5). This dose was also able to prevent scopolamine related amnesia in healthy young humans (15)

For nootropic purposes, 300mg taken once or twice per day seems a reasonable starting point.

Relevant Articles

  1. Which Choline Source Is Best?
  2. Good Starting Stacks For Newcomers


GPC appears to be mostly hydrolysed (broken down) in the gut via phosphodiesterase into various metabolites such as glycerophosphate, choline and phosphorylcholine. One study in rodents using radiolabeled Alpha GPC showed various choline metabolites to be formed following oral administration (1). The authors remarked in the discussion that each of these metabolites likely have their own abortion, tissue distribution and elimination profiles.

In contrast to this, another rodent study showed that intraperitoneal injection of GPC was able to reduce age related decreases in acetylcholine receptors whereas GPC metabolites (glycerophosphate, choline and phosphorylcholine) were not able to do the same. (2)

Since it’s known that Alpha GPC can cross the blood brain barrier intact (1), and that GPC is superior to choline in improving clinical symptoms (3), it’s reasonable to assume that some of an oral dose is absorbed intact and crosses the blood brain barrier.

Looking at the research there’s no clear study in humans that shows GPC by mouth goes straight into the brain, but empirically we know that GPC is superior to lecithin derived choline at improving cognitive function. We also know that GPC in rodents can cross the BBB and that its metabolites are inferior to the whole molecule. From this it’s safe to assume some oral GPC is absorbed intact and crosses the BBB in humans.

Benefits of Alpha GPC

Memory and Learning

One study involving young healthy rodents showed that GPC improved learning in an active avoidance task. (6)

Active avoidance is where rodents are subjected to a small shock following a stimulus, such as a sound playing. The rats are typically presented with an escape compartment to avoid the shock. The quicker the rats learn that the sound = incoming shock, the better it performs. Administration of GPC increased the number of times the rats avoided shock and also decreased the latency, i.e. the time it took them to do so.

Another rodent study showed GPC was able to reduce the amnesiac effects of scopolamine, a potent anticholinergic drug. Its hypothesised GPC did so by increasing acetylcholine synthesis. (7)

In humans two trials have shown GPC is able to reduce scopolamine induced cognitive deficits in young healthy volunteers. (15)(16) Interestingly, GPC was unable to protect against benzodiazepine induced amnesia, supporting the idea that GPC’s cognitive enhancement effects are mediated through acetylcholine synthesis and cholinergic mechanisms.

GPC appears to be prevent the amnesiac effects that typically occur when scopolamine (a potent anti-cholinergic) is administered. Currently the two human trials aren’t available online, though both are discussed vicariously through reference 16. Perhaps the key take home point was that GPC was able to increase cognitive function above baseline for young healthy subjects, a “holy grail” of any nootropic.

Cognitive Decline (Alzheimer’s and Dementia)

A large meta-analysis involving 1570 patients across 10 clinical studies concluded that GPC significantly improves patient conditions, as assessed by mini mental state examination (MMSE) and sandoz clinical assessment geriatric scale (SGAG) (5)(9)(14). Both MMSE and SCAG are frequently used to assess cognitive impairment in patients with dementia.

brain scan

Muscular Power and Growth Hormone

One small pilot study involving 7 men showed increased peak force output in the bench by 14% following ingestion of 600mg Alpha GPC (4). The study also noted a significant elevation in growth hormone.

A second study involving 8 males showed 1000mg of Alpha GPC was able to significantly increase growth hormone and markers of fat oxidation (8)


Alpha GPC’s Mechanism Of Action

Cell Membrane Synthesis and Maintenance

Alpha GPC increases brain choline content. As choline is a required building block for cell membranes it’s no surprise that Alpha GPC supports cell membrane upkeep by increasing the brain’s supply of choline.

Research involving young and aged rats showed chronic treatment of GPC (200mg/KG) was able to restore muscarinic receptor density (specifically M1) to youthful levels in both the hippocampus and striatum (2). A similar study also found GPC was able to partially restore M1 muscarinic density to youthful levels. (10)

Research also indicates GPC is partially able to restore cell membrane fluidty (in part) to youthful levels in the striatum and hippocampus. (10)

Neurotransmitter Synthesis

Alpha GPC produced when cell membranes are taken apart for their choline content, a process known as auto cannibalisation (18)(19). It’s no stretch then, that oral GPC supplements support acetylcholine synthesis by providing the brain with the raw materials.



Increasing Cholinergic Transporters

A seven day treatment of 150mg/kg a day Alpha-GPC found GPC increased frontal cortex acetylcholine concentration. The research indicated that cholinergic transporters VAChT (Vesicular acertylcholine transporter) and ChAT (choline acetyltransferase) were significantly expressed more in both the striatum and cerebellum following GPC. (11) Further research showed 100mg/KG GPC restored AhCE (acetylcholinesterase) to more youthful levels in aged rats. (12)

Supporting Acetylcholine Synthesis

4 studies in total have been conducted with GPC and the anticholinergic drug scopolamine.  Two involving rodents showed GPC was able to prevent scopolamine induced amnesia by supporting acetycholine synthesis (7)(13)

A study involving 32 healthy human volunteers showed 10 day pre-treatment with GPC was superior to placebo at blocking the negative cognitive effects of scopolamine.  The dosage used was 1200mg per day. Specifically GPC was able to help maintain attention scores and improve word recall. Interestingly GPC improved baseline performance for the word recall test, suggesting cognitive enhancement in young healthy individuals (15). (Full paper unavailable online, though abstract available and paper is discussed here (

The same researchers conducted a second study involving 48 young men and women. Volunteers were pre-treated with either; GPC (1200mg/Day), idebenone or aniracetam for 7 days.  Cognitive performance, particularly in verbal memory and working memory was significantly protected by GPC.  Alpha-GPC was found to be superior to aniracetam and idebenone in these respects.   (Full paper unavailable online, paper is discussed in ref 16)


Safety and Side Effects

GPC appears to be a remarkably safe nootropic that processes few-little side effects in the therapeutic dose range.  One trial reported side effects in 2.4% of all patients, which consisted by mainly of nausea (0.5%), heartburn (0.7%) and insomnia (0.4%) at a dose of 1200mg/day. (17)

The LD50 for GPC is 10,000mg / Kilo for rodents when administered orally. A drop in food consumption and increase in bodyweight was noted in rodents at a dose of 1000mg/kg. (17)





Original article @smarternootropics

The Balanced Macro Diet

When you first begin training, it becomes almost immediately apparent that you will need to eat well if you’re going to reach your goals. But how much protein should you be eating each day? Should you be eating high carb and low fat? Some say that you should be eating twice as many calories from carbohydrates as protein. Others suggest a more balanced ratio. What worked for me was to start by consuming the same amount of calories from each macronutrient. This formula will get many of you pretty damn far.

How many total calories will you need each day to support your metabolism and fuel the addition of new muscle tissue? Don’t worry because I am going to make it incredibly simple for you. Follow the easy steps outlined below and you will be on your way to a sensible, balanced diet that will help you get started…and then some. All you need to know is your body weight.


Read the full article by Evan Centopani @animal




PRL-8-53 Overview


PRL-8-53 is a nootropic research compound first synthesized in the 1970’s by Dr Nikolaus Hansl while working at Creighton University. The compound takes its name from creator’s company Pacific Research Labs (3) who were also the (now expired) patent holders (3). Very little research on this compound is available online. What is available appears to have been conducted by the old patent holder.

The single study involving humans showed PRL-8-53 improved word recollection scores both 24 and 96 hours after initial memorization. Given the low amount of evidence available for this nootropic, we thought it relevant to reference a journal article in which the creator discusses the compound and numerous other human trials it was used in.

Anecdotal reports for this seem favorable, though in the absence of reliable published research and data for prolonged use in humans, it’s not something we can recommend.

Other Names:

Methyl 3-[2-[benzyl(methyl)amino]ethyl]benzoate hydrochloride


Important Information


PRL-8-53 In A Nootropic Stack

The limited research for this nootropic suggests that it’s memory enhancing. The compound creator also discusses other benefits, which we cover below. Given the low amount of research on this compound and an unknown mechanism of action, we can’t advise on what to stack this with. If you do decide to experiment with it, consider taking PRL-8-53 without other nootropics to reduce possible interactions.

Dosing PRL-8-53

The single published human study used 5mg of PRL-8-53 and found it enhanced recall on a word-remembering test. (1) The patent for the compound mentions an oral dose of 0.01mg/kg per dose, taken 3 times per day. (3)

PRL-8-53’s Structure and Absorption

PRL-8-53 is derived from benzoic acid and phenylmethylamine. The compound is a benzoic acid methyl ester.  We’re unable to find any absorption data for this compound, though it can be assumed to cross the blood brain barrier.


Benefits of PRL-8-53



The single published study for PRL-8-53 shows a slight improvement of word acquisition during a memorization task. Participants were given 5mg of PRL-8-53 2 hours prior to testing and then were then asked to listen to a recording of 12 words in a particular sequence and recite them at future time points (shortly after testing, a day after and 4 days after). Minor benefits were found for immediate acquisition, but an over 80% improvement was noted for people tested later on who had initially scored poorly for the test (6/12 words correctly or below) [1].

Unpublished (Possible) Benefits – Geometric Pattern Exercise

Interestingly, the compound creator also discusses other trials which appear to be unavailable or unpublished. In a Journal published in 1978, Dr Hansl mentions that PRL-8-53 statistically improved scores in a geometric pattern cognitive exercise. Participants were shown a series of geometric patterns and ask to draw them from memory, a statistical improvement was noted.

Mental Arithmetic Exercise

In the same article, Dr Hansl mentions a number based cognitive exercise where participants had to subtract 7, add 1, subtract 7, add 2 and so on until a “goal” number was reached. Shorter times to the “goal” number were noted in the PRL-8-53 group.

Verbal Fluency Test

Dr Hansl discusses a test where subjects were asked to form words from a series of letters and dots. For example “U.R.” had to be turned into any word by adding letters at the start and end of the word, while replacing the dots with a letter. “U.R.” could be “current” for example. A statistically significant improvement was found in participants who had taken the drug.

It should be noted that all of the discussed “possible” benefits are sourced from an article (4) in 1978 where Dr Hansl was discussing the compound. Sadly, Dr Hansl passed away in 2011 We are unable to find published research that proves or disproves these claims

PRL-8-53’s Mechanism Of Action


The mechanism of action for this nootropic is currently unknown but may, in part, lie with cholinergic mechanisms. Dr Hansl, the creator of the compound discusses in the Phi Delta Kappan journal that PRL-8-53 enhances brain’s the response to acetylcholine, and the compound is not a stimulant (4). The patent for PRL-8-53 mentions cholinergic mechanisms. (3)

An animal test involving rodents showed 4mg/KG increased apomorphine (dopamine agonist) increased compulsive gnawing in rats, suggesting that PRL-8-53 to some extent is a dopamine agonist (2). The same study noted an improvement in conditioned avoidance learning. This nootropic does not enhance amphetamine’s actions in rats and doesn’t appear inhibit MAO activity. (2) The single study in humans briefly mentions that PRL-8-53 potentiates dopamine release and causes partial inhibition of serotonin (1).


PRL-8-53 Safety and Side Effects

The LD-50 for this nootropic is 800mg/KG in rodents (2) and reduced motor activity has been noted at 100mg/kg in mice. In human trials, the 5mg dosage used noted no side effects (1). The patent for PRL-8-53 mentions the compound is well tolerated in dogs and monkeys at 50mg/kg.





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Original article@smarternootropics




IDRA-21 is a relatively new nootropic compound. It works as an ampakine stimulant drug and is currently being researched in regards to its effects in memory improvement, cognitive enhancement, stimulation, and reversing cognitive deficits. It’s likely it was developed in 1994 or 1995 as the first clinical trials and peer-reviewed research articles appear in the literature in 1995.

Other Names

IDRA-21, 7-chloro-3-methyl-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide, C8H9ClN2O2S

IDRA-21 In A Nootropic Stack

Due to potential AMPAkine excitotoxicity, it is not recommended to combine IDRA-21 with other ampakine drugs such as Aniracetam. Little is known about toxicity in humans. Other Nootropics which increase glutamate should be avoided as well.

IDRA-21 Dosing

IDRA-21 currently has only had animal trials. Dosing in a study with Patas Monkeys was 3 or 5.6 mg/kg p.o. in addition with 30 mg/kg p.o. of Aniracetam[1]. This study indicated that IDRA-21 was 10-fold more potent than Aniracetam at reducing learning defects. A water maze study in rats showed cognitive enhancement at oral dosages of 4-120 mumol/kg[5].

Human dosages have no history of peer-reviewed clinical studies. Some reading online suggested positive human activity at 5-25mg orally[2].

IDRA-21 Structure

IDRA-21 is a benzothiazone derivative. It’s structurally unrelated to Aniracetam, another ampakine drug. It’s a chiral molecule, with the dextrorotary isomer being the active form[6].

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IDRA-21 Absorption

There is very little information about absorption rates. Most rat and monkey studies determined efficacy with oral dosing, which would seem to indicate that oral is an effective route.

IDRA-21 Benefits

  • Increases in cognition (Matching sample tasks performed by Rhesus Monkeys)[7]

  • Increased Task Accuracy[7]

  • Increases in Short Term Memory[8]

  • Potential Therapeutic Effects On Schizophrenia[8]

  • Potental Therapeutic Effects On Depression[8]

  • Neuroprotection[5]

  • Benefits Against Alprazolam-induced Cognitive Deficit[1]

IDRA-21 Mechanism Of Action

IDRA belongs to a class of compounds known as ampakines. Ampakines are allosteric modulators of AMPA receptors in the brain. AMPA receptors are responsible for fast synaptic transmission [9] and are implicated in synaptic plasticity and long term potentiation [10].

As an Ampakine, IDRA-21 works by modulating AMPA receptors in the brain. Specifically IDRA-21 binds to the allosteric site of the AMPA receptor and induce positive modulation, this is sometimes called allosteric activation.

Initial research on IDRA-21 suggests that it may prevent AMPA receptor desensitization (1) and therefore increase synaptic responses and support memory and learning.

IDRA-21 Safety and Side Effects

IDRA-21 is a potent Ampakine. AMPA activation has been shown to exacerbate hippocampal neural damage[3]. IDRA-21 when administered with glutamate killed rat hippocampal neurons through AMPA excitoxicity[3]. This is potentially dangerous in patients with conditions that excessively activate AMPA such as strokes and seizures.

In another study, the dosages of IDRA-21 that induced neurotoxicity were several orders of magnitude higher than the doses that achieved cognitive enhancement in rats and monkeys, leading the researchers to conclude that IDRA-21 has relatively low neurotoxicity in therapeutic doses[4].