The Iowa State University Gregory A. Brown, MS Is ...

1 "Muscle Building" Nutritional Supplements: Is Androstenedione An Anabolic Steroid?"Muscle Building" Nutritional Supplements: Is Androstenedione An Anabolic Steroid?Exercise Biochemistry LaboratoryDept. of Health & Human PeformanceThe iowa State UniversityExercise Biochemistry LaboratoryDept. of Health & Human PeformanceThe iowa State UniversityGregory A. Brown, MSGregory A. Brown, MSRoger Maris61 Home Runs in a Season1961 Roger Maris61 Home Runs in a Season1961 Mark McGwire70 Home Runs in a Season1998 Mark McGwire70 Home Runs in a Season1998 Time After Ingestion (min)03060900 Serum androgen levels after intake of 100 mg Androstenedionein Two Women(nM)0108642 AndrostenedioneAndrostenedione(nM)481216 2024 Total TestosteroneTotal Testosterone(Mahesh & Greenblatt, 1962)(Mahesh & Greenblatt, 1962)

2 Androgen and Estrogen RelationsAndrogen and Estrogen RelationsA = P 450 Side Chain Cleavage B= 3 hydroxysteroid dehydrogenaseC = 17 hydroxylase D = P450 17, 20 lysaseE = P450 aromataseF = 17 hydroxysteroid oxidoreductaseG = 5 reductaseH = ketoreductaseA = P 450 Side Chain Cleavage B= 3 hydroxysteroid dehydrogenaseC = 17 hydroxylase D = P450 17, 20 lysaseE = P450 aromataseF = 17 hydroxysteroid oxidoreductaseG = 5 reductaseH = ketoreductaseAndrostenedioneAndrostenedi oneTestosteroneTestosteroneFDHEA-SDHEA-S DHEADHEABA ndrostenedioneAndrostenedioneDHTDHTEGGGG 3 -Androstanediol3 -Androstanediol3 -Androstanediol3 -AndrostanediolHEstradiol (E2)Estradiol (E2)Estrone (E1)Estrone (E1)DEEstriol (E3) Estriol (E3) FDoes acute androstenedione intake alter serum hormone concentrations in young men?

3 Does acute androstenedione intake alter serum hormone concentrations in young men?Time After Intake (min)060120180240300360 Serum Androstenedione (nM)10152025303540*vs baseline (P< )*100 mg et al, 1999 King et al, 1999 PLASD**Total Testosterone(nM)020406080100 Free Testosterone(pM)481216202428 PLASD060120180240300360 Time After Intake (min)100 mg et al, 1999 King et al, 1999 Does Chronic Androstenedione Intake Enhance The Gains In Muscle Size and Strength During Resistance Training?Does Chronic Androstenedione Intake Enhance The Gains In Muscle Size and Strength During Resistance Training?King et al, 1999 King et al, 1999 20 untrained subjects Male (~23 y) No current/previous supplement or steroid use 8 weeks full body resistance training 3 days/week 80-85% 1 RM Random, double blind PL (rice flour) Androstenedione (100 mg ) 20 untrained subjects Male (~23 y) No current/previous supplement or steroid use 8 weeks full body resistance training 3 days/week 80-85% 1 RM Random, double blind PL (rice flour) Androstenedione (100 mg )WEEKS24680 SupplementationBloodChemistryBodyComposi tion1 RMTestingSex HormonesKing et al, 1999 King et al, 1999 Muscle Biopsy05001000150020002500 Lower body StrengthKnee Ex + R.

4 Leg Flexion + L. Leg Flexion (N)BeforeTrainingAfterTrainingBeforeTrai ningAfterTraining**PlaceboAndrostenedion eKing et al, 1999 King et al, 1999 Lean body Mass (kg)3040506070 BeforeTrainingAfterTrainingBeforeTrainin gAfterTrainingPlaceboAndrostenedione**Ki ng et al, 1999 King et al, 1999 PLASDUNType I Area ( m2)Type II Area ( m2)0100020003000400050006000700001000200 030004000500060007000**TRUN TRPLASDUN TRUN TRKing et al, 1999 King et al, 1999 Weeks of Supplementation24680 Androstenedione (nM)**51015202530350 PlaceboAndrostenedioneKing et al, 1999 King et al, 1999 FreeTestosterone (pM)TotalTestosterone (nM)Weeks of Supplementation2468008010012014060402001 602024283216128436 King et al, 1999 King et al, 1999 PlaceboAndrostenedioneIs Androstenedione Intake Safe?

5 Is Androstenedione Intake Safe?(mg/dL)24262830323436384042444648 BeforeTrainingAfterTraining*BeforeTraini ngAfterTrainingPlaceboAndrostenedioneHDL -CholesterolKing et al, 1999 King et al, 1999 Weeks of Supplementation24680 Estrone (E1:pM)**7017090110130150 Estradiol (E2: nM) ** *Estriol (E3:nM) et al, 1999 King et al, 1999 PlaceboAndrostenedioneOther Notable FindingsOther Notable FindingsControlAndrostenedione% Post Rassmussen et al, 2000 Rassmussen et al, 2000 Effect of 100 mg androstenedione/day on Muscle Protein Fractional Synthetic RateEffect of 100 mg androstenedione/day on Muscle Protein Fractional Synthetic RatePre Post 18001600140012001000800600400200 Testosterone (ng/dL)BaselineBaselinePeakPeak100 mgAndrostenedione300 mgAndrostenedioneP= et al, 2000 Leder et al, 2000No ChangeEffect of 100 mg androstenedione in different agesEffect of 100 mg androstenedione in different ages406080100120406080100120 Serum Free Testosterone (pM)

6 40608010012030 year olds40 year olds50 year oldsWeek01234** Brown et al, 2000 Brown et al, 2000PL ASD 10002000300040005000 Dihydrotestosterone (pM)100020003000400050001000200030004000 5000 Week0123430 year olds40 year olds50 year oldsPL ASD ** Effect of 100 mg androstenedione in different agesEffect of 100 mg androstenedione in different agesBrown et al, 2000 Brown et al, 2000 Chronic androstenedione intake in doses up to 100 mg does not enhance The increase in muscle mass and strength associated with resistance training Serum testosterone Muscle protein synthesis Chronic androstenedione intake in doses up to 100 mg does not enhance The increase in muscle mass and strength associated with resistance training Serum testosterone Muscle protein synthesisTo SummarizeTo Summarize Chronic androstenedione intake in doses up to 100 mg does Increase Serum Dihydrotestosterone Increase Serum Estrogens Decrease Serum HDL-C Chronic androstenedione intake in doses up to 100 mg does Increase Serum Dihydrotestosterone Increase Serum Estrogens Decrease Serum HDL-CTo SummarizeTo SummarizePossible Adverse Health ConsequencesPossible

7 Adverse Health ConsequencesLowered HDL-C Increased CV disease risk by 10-15%Elevated Estrogens Have been linked Increased CV disease risk Pancreatic Cancer GynecomastiaLowered HDL-C Increased CV disease risk by 10-15%Elevated Estrogens Have been linked Increased CV disease risk Pancreatic Cancer GynecomastiaPossible Adverse Health ConsequencesPossible Adverse Health ConsequencesElevated Androstenedione may be associated Prostate Cancer Pancreatic Cancer Neural/BehavioralElevated Dihydrotestosterone has been linked Benign Prostate Hypertrophy BaldnessElevated Androstenedione may be associated Prostate Cancer Pancreatic Cancer Neural/BehavioralElevated Dihydrotestosterone has been linked Benign Prostate Hypertrophy BaldnessCompoundDaily DosePurposeSaw Palmetto480 mg Reduce DHT metabolism/ bindingInhibit 5 reductaseIndole-3-Carbinol450 mgInhibit formation of estrogensTribulus Terristris1,350 mgIncrease LH, FSH, Testosterone Linolenic Acid1500 mgInhibit 5 reductaseChrysin300 mg Inhibit aromatizationCompoundDaily DosePurposeSaw Palmetto480 mg Reduce DHT metabolism/ bindingInhibit 5 reductaseIndole-3-Carbinol450 mgInhibit formation of estrogensTribulus Terristris1,350 mgIncrease LH, FSH, Testosterone Linolenic Acid1500 mgInhibit 5 reductaseChrysin300 mg Inhibit aromatizationHerbal ExtractsHerbal ExtractsBrown et al, 2000 and 2001 Brown et al, 2000 and 2001 Does not prevent formation of estrogens from androstenedione.

8 And Does not increase serum testosterone levels. Does not prevent formation of estrogens from androstenedione, and Does not increase serum testosterone of These Herbal ExtractsAddition of These Herbal ExtractsBrown et al, 2000 and 2001 Brown et al, 2000 and 2001 Future DirectionsFuture Directions To what extent do greater (>300 mg/d) doses of androstenedione affect serum testosterone, muscle strength and size? To what extent do greater (>300 mg/d) doses of androstenedione affect serum testosterone, muscle strength and size?Future DirectionsFuture Directions What are the long term health consequences of prolonged androstenedione intake? Cardiovascular Risk Fertility What are the long term health consequences of prolonged androstenedione intake? Cardiovascular Risk FertilityFuture DirectionsFuture Directions What are the effects of age and gender on modifying the response to androstenedione?

9 What are the effects of alternative modes of delivery? What are the effects of age and gender on modifying the response to androstenedione? What are the effects of alternative modes of delivery?Future DirectionsFuture Directions What are the effects of other androcompounds? What are the effects of combining various forms of andro? What are the effects of other androcompounds? What are the effects of combining various forms of andro?Matthew D. Vukovich, PhD Rick L. Sharp, PhDMarian L. Kohut, PhDWarren D. Franke, PhDTracy A. Reifenrath, A. Parsons, A. Jackson, Uhl, R. Martini, Douglas S. King, PhDMatthew D. Vukovich, PhD Rick L. Sharp, PhDMarian L. Kohut, PhDWarren D. Franke, PhDTracy A. Reifenrath, A. Parsons, A. Jackson, Uhl, R. Martini, Douglas S.

10 King, PhDWe are grateful toWe are grateful toFor their their support. Chronic androstenedione intake in doses up to 100 mg does not alter serum concentrations of Low Density Lipoprotein Very Low Density Lipoprotein Gamma-glutamyltransferase Aspartate aminotransferase Alanine aminotransferase Globulins Proteins Prostate Specific AntigenKing et al, 1999 and Brown et al, 2000 King et al, 1999 and Brown et al, 2000 Extra Summary of Other Clinical FindingsExtra Summary of Other Clinical Findings A single 100-200 mg dose of androstenedione does not increase serum serum concentrations of testosterone in young men. A single 300 mg dose of androstenedione may slightly increase serum concentrations of testosteroneExtra SummaryExtra Summary Chronic androstenedione intake in doses up to 100 mg doesnotenhance Serum testosterone Muscle protein synthesis Adaptations to resistance training lean mass fat mass muscle fiber size muscle strengthKing et al, 1999 King et al, 1999 Extra SummaryExtra SummaryLH (mIU/ml)FSH mIU/ml)123456234567100 Weeks of Supplementation24680 PLASDE xtra training dataExtra training dataWeeks of Supplementation2468010203040500 Serum HDL (mg/dL)PlaceboAndrostenedione**Extra training dataExtra training data204060801001201400 Weeks of Supplementation24680 PLASDS erum LDL (mg/dL)