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Is Androstenedione an Anabolic Steroid? "Muscle Building" Nutriti

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Is Androstenedione an Anabolic Steroid? "Muscle"Muscle Building"Building" NutritionalNutritional Supplements:Supplements: IsIs AndrostenedioneAndrostenedione AnAn AnabolicAnabolic Steroid?Steroid? GregoryGregory A.A. Brown,Brown, MSMS ExerciseExercise BiochemistryBiochemistry LaboratoryLaboratory Dept.Dept. ofof HealthHealth && HumanHuman PeformancePeformance TheThe IowaIowa StateState UniversityUniversity RogerRoger MarisMaris MarkMark McGwireMcGwire 6161 HomeHome RunsRuns inin aa SeasonSeason 7070 HomeHome RunsRuns inin aa SeasonSeason 19611961 19981998 Serum androgen levels after intake of 100 mg Androstenedione in Two Women 10 8 6 (nM) Androstenedione 4 2 0 24 20 16 Total Testosterone (nM) 12 8 4 0 0306090 (Mahesh(Mahesh && Greenblatt, Greenblatt, 1962)1962) Time After Ingestion (min) AndrogenAndrogen andand EstrogenEstrogen RelationsRelations D B E DHEA-SDHEA-S DHEADHEA AndrostenedioneAndrostenedione EstroneEstrone (E(E11)) F G E G G F G DHTDHT TestosteroneTestosterone EstradiolEstradiol (E(E22)) H 33ββ-- 33αα-- AndrostanediolAndrostanediol AndrostanediolAndrostanediol EstriolEstriol (E(E33)) AA == PP 450450 SideSide ChainChain CleavageCleavage B=B= 33 ββ hydroxysteroidhydroxysteroid dehydrogenasedehydrogenase CC == 1717 αα hydroxylasehydroxylase DD == P450P450 17,17, 2020 lysaselysase EE == P450P450 aromatasearomatase F F == 1717 ββ hydroxysteroidhydroxysteroid oxidoreductase oxidoreductase GG == 55 αα reductasereductase H H == ketoreductaseketoreductase DoesDoes acuteacute androstenedioneandrostenedione intakeintake alteralter serumserum hormonehormone concentrationsconcentrations inin youngyoung men?men? * vs baseline (P<0.05) 40 * * * * * * * 35 * 30 * * 25 * PL ASD 20 100 mg Andro. 15 10 Serum Androstenedione (nM) 5 0 0 60 120 180 240 300 360 KingKing etet al,al, 19991999 Time After Intake (min) 100 80 60 (pM) 40 20 PL Free Testosterone ASD 0 28 100 mg Andro. 24 20 16 (nM) 12 8 4 Total Testosterone Total 0 60 120 180 240 300 360 KingKing etet al,al, 19991999 Time After Intake (min) DoesDoes ChronicChronic AndrostenedioneAndrostenedione IntakeIntake EnhanceEnhance TheThe GainsGains InIn MuscleMuscle SizeSize andand StrengthStrength DuringDuring ResistanceResistance Training?Training? KingKing etet al,al, 19991999 •• 2020 untraineduntrained subjectssubjects –– MaleMale (~23(~23 y)y) –– NoNo current/previouscurrent/previous supplementsupplement oror steroidsteroid useuse •• 88 weeksweeks fullfull bodybody resistanceresistance trainingtraining •• 33 days/weekdays/week •• 80-85%80-85% 11 RMRM •• Random,Random, doubledouble blindblind –– PLPL (rice(rice flour)flour) –– AndrostenedioneAndrostenedione (100(100 mgmg t.i.dt.i.d)) 1 RM Testing Body Composition Blood Chemistry Sex Hormones Muscle Biopsy Supplementation 0 2468 KingKing etet al,al, 19991999 WEEKS 2500 Placebo Androstenedione * 2000 * 1500 1000 Lower Body StrengthLower Body 500 Knee Ex + R. Leg Flexion + L. Leg Flexion (N) Leg Flexion + L. Leg Flexion + R. Knee Ex 0 Before After Before After Training Training Training Training KingKing etet al,al, 19991999 Placebo Androstenedione 70 * * 60 50 40 Lean Body Mass (kg) 30 Before After Before After Training Training Training Training KingKing etet al,al, 19991999 7000 7000 * 6000 6000 * 5000 ) ) 5000 2 2 m m µ µ µ µ µ µ 4000 µ µ 4000 3000 3000 Type I Area ( 2000 2000 Type II Area ( 1000 1000 0 0 UN TR UN TR UN TR UN TR PL ASD PL ASD KingKing etet al,al, 19991999 Placebo 35 Androstenedione 30 * * 25 20 15 10 Androstenedione (nM) 5 0 0 2468 KingKing etet al,al, 19991999 Weeks of Supplementation 160 140 120 100 80 Free 60 40 Placebo 20 Androstenedione Testosterone (pM) 0 36 32 28 24 20 16 Total 12 8 4 Testosterone (nM) 0 0 2468 KingKing etet al,al, 19991999 Weeks of Supplementation IsIs AndrostenedioneAndrostenedione IntakeIntake Safe?Safe? 48 Placebo Androstenedione 46 44 42 * 40 38 36 (mg/dL) 34 HDL-Cholesterol 32 30 28 26 24 Before After Before After Training Training Training Training KingKing etet al,al, 19991999 Placebo 170 * * Androstenedione 150 :pM) 1 130 110 90 Estrone (E 70 0.4 * * : nM) * 2 0.3 0.2 0.1 Estradiol (E 0.0 0.4 0.3 :nM) 3 0.2 0.1 Estriol (E 0.0 0 2468 KingKing etet al,al, 19991999 Weeks of Supplementation OtherOther NotableNotable FindingsFindings EffectEffect ofof 100100 mgmg androstenedione/dayandrostenedione/day onon MuscleMuscle ProteinProtein FractionalFractional SyntheticSynthetic RateRate 0.14 0.12 Control Androstenedione 0.10 0.08 %/hour 0.06 0.04 0.02 0.00 Pre Post Pre Post RassmussenRassmussen et et al,al, 20002000 1800 1600 P=0.001 1400 1200 No Change 1000 800 600 Testosterone (ng/dL) 400 200 Baseline Peak Baseline Peak 100 mg 300 mg Androstenedione Androstenedione LederLeder etet al,al, 20002000 EffectEffect ofof 100100 mgmg androstenedioneandrostenedione t.i.d.t.i.d. inin differentdifferent agesages 120 30 year olds 100 80 60 PL 40 ASD 120 40 year olds 100 80 60 40 120 50 year olds 100 Serum Free Testosterone (pM) Testosterone Free Serum 80 60 40 ‡ **** Brown et al, 2000 01234 Brown et al, 2000 Week EffectEffect ofof 100100 mgmg androstenedioneandrostenedione t.i.d.t.i.d. inin differentdifferent agesages 5000 30 year olds 4000 3000 2000 1000 5000 40 year olds PL 4000 ASD 3000 2000 1000 5000 50 year olds 4000 Dihydrotestosterone (pM) Dihydrotestosterone 3000 2000 1000 ‡ **** 01234 BrownBrown etet al,al, 20002000 Week ToTo SummarizeSummarize •• ChronicChronic androstenedioneandrostenedione intakeintake inin dosesdoses upup toto 100100 mgmg t.i.d.t.i.d. doesdoes notnot enhanceenhance •• TheThe increaseincrease inin musclemuscle massmass andand strengthstrength associatedassociated withwith resistanceresistance trainingtraining •• SerumSerum testosteronetestosterone •• MuscleMuscle proteinprotein synthesissynthesis ToTo SummarizeSummarize •• ChronicChronic androstenedioneandrostenedione intakeintake inin dosesdoses upup toto 100100 mgmg t.i.d.t.i.d. doesdoes •• IncreaseIncrease SerumSerum DihydrotestosteroneDihydrotestosterone •• IncreaseIncrease SerumSerum EstrogensEstrogens •• DecreaseDecrease SerumSerum HDL-CHDL-C PossiblePossible AdverseAdverse HealthHealth ConsequencesConsequences LoweredLowered HDL-CHDL-C •• IncreasedIncreased CVCV diseasedisease riskrisk byby 10-15%10-15% ElevatedElevated EstrogensEstrogens HaveHave beenbeen linkedlinked to…to… •• IncreasedIncreased CVCV diseasedisease riskrisk •• PancreaticPancreatic CancerCancer •• GynecomastiaGynecomastia PossiblePossible AdverseAdverse HealthHealth ConsequencesConsequences ElevatedElevated AndrostenedioneAndrostenedione maymay bebe associatedassociated with…with… •• ProstateProstate CancerCancer •• PancreaticPancreatic CancerCancer •• Neural/BehavioralNeural/Behavioral ElevatedElevated DihydrotestosteroneDihydrotestosterone hashas beenbeen linkedlinked to…to… •• BenignBenign ProstateProstate HypertrophyHypertrophy •• BaldnessBaldness HerbalHerbal ExtractsExtracts CompoundCompound Daily Daily DoseDose Purpose Purpose SawSaw PalmettoPalmetto 480 480 mgmg ReduceReduce DHTDHT metabolism/metabolism/ bindingbinding InhibitInhibit 55 αα reductasereductase IndoleIndole-3-3-C-Carbinolarbinol 450 450 mgmg Inhibit Inhibit formationformation ofof estrogensestrogens TribulusTribulus Terristris Terristris 1,350 1,350 mgmg Increase Increase LH,LH, FSH,FSH, TestosteroneTestosterone γγ LinolenicLinolenic AcidAcid 1500 1500 mgmg Inhibit Inhibit 55 αα reductasereductase ChrysinChrysin 300 300 mgmg InhibitInhibit aromatizationaromatization BrownBrown etet al,al, 20002000 andand 20012001 AdditionAddition ofof TheseThese HerbalHerbal ExtractsExtracts •• DoesDoes notnot preventprevent formationformation ofof estrogensestrogens fromfrom androstenedione,androstenedione, andand •• DoesDoes notnot increaseincrease serumserum testosteronetestosterone levels.levels. BrownBrown etet al,al, 20002000 andand 20012001 FutureFuture DirectionsDirections •• ToTo whatwhat extentextent dodo greatergreater (>300(>300 mg/d)mg/d) dosesdoses ofof androstenedioneandrostenedione affectaffect serumserum testosterone,testosterone, musclemuscle strengthstrength andand size?size? FutureFuture DirectionsDirections •• WhatWhat areare thethe longlong termterm healthhealth consequencesconsequences ofof prolongedprolonged androstenedioneandrostenedione intake?intake? •• CardiovascularCardiovascular RiskRisk •• FertilityFertility FutureFuture DirectionsDirections •• WhatWhat areare thethe effectseffects ofof ageage andand gendergender onon modifyingmodifying thethe responseresponse toto androstenedione?androstenedione? •• WhatWhat areare thethe effectseffects ofof alternativealternative modesmodes ofof delivery?delivery? FutureFuture DirectionsDirections •• WhatWhat areare thethe effectseffects ofof otherother androandro compounds?compounds? •• WhatWhat areare thethe effectseffects ofof combiningcombining variousvarious formsforms ofof andro?andro? MatthewMatthew D.D. Vukovich,Vukovich, PhDPhD RickRick L.L. Sharp,Sharp, PhDPhD MarianMarian L.L. Kohut, Kohut, PhDPhD WarrenWarren D.D. Franke, Franke, PhDPhD TracyTracy A.A. Reifenrath,Reifenrath, M.S.M.S. KerryKerry A.A. Parsons,Parsons, M.S.M.S. DavidDavid A.A. Jackson,Jackson, M.S.M.S. N.L.N.L. Uhl,Uhl, B.S.B.S. EmilyEmily R.R. Martini,Martini, B.S.B.S. DouglasDouglas S.S. King,King, PhDPhD WeWe areare gratefulgrateful toto ForFor theirtheir support. support. ExtraExtra SummarySummary ofof OtherOther ClinicalClinical FindingsFindings • Chronic androstenedione intake in doses up to 100 mg t.i.d. does not alter serum concentrations of – Low Density Lipoprotein – Very Low Density Lipoprotein – Gamma-glutamyltransferase – Aspartate aminotransferase – Alanine aminotransferase
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